共查询到20条相似文献,搜索用时 46 毫秒
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Rafael González-Castro Prof. Miguel A. Gómez-Lim Dr. Fabien Plisson 《Chembiochem : a European journal of chemical biology》2021,22(6):961-973
Cysteine-rich peptides (CRPs) are small proteins of less than 100 amino acids in length characterized by the presence of disulfide bridges and common end-to-end macrocyclization. These properties confer hyperstability against high temperatures, salt concentration, serum presence, and protease degradation to CRPs. Moreover, their intercysteine domains (loops) are susceptible to residue hypervariability. CRPs have been successfully applied as stable scaffolds for molecular grafting, a protein engineering process in which cysteine-rich structures provide higher thermodynamic and metabolic stability to an epitope and acquire new biological function(s). This review describes the successes and limitations of seven cysteine-rich scaffolds, their bioactive epitopes, and the resulting grafted peptides. 相似文献
3.
Dr. Teshome L. Aboye Dr. Adam A. Strömstedt Dr. Sunithi Gunasekera Dr. Jan G. Bruhn Dr. Hesham El‐Seedi Dr. K. Johan Rosengren Dr. Ulf Göransson 《Chembiochem : a European journal of chemical biology》2015,16(7):1068-1077
Naturally occurring cystine knot peptides show a wide range of biological activity, and as they have inherent stability they represent potential scaffolds for peptide‐based drug design and biomolecular engineering. Here we report the discovery, sequencing, chemical synthesis, three‐dimensional solution structure determination and bioactivity of the first cystine knot peptide from Cactaceae (cactus) family: Ep‐AMP1 from Echinopsis pachanoi. The structure of Ep‐AMP1 (35 amino acids) conforms to that of the inhibitor cystine knot (or knottin) family but represents a novel diverse sequence; its activity was more than 500 times higher against bacterial than against eukaryotic cells. Rapid bactericidal action and liposome leakage implicate membrane permeabilisation as the mechanism of action. Sequence homology places Ec‐AMP1 in the plant C6‐type of antimicrobial peptides, but the three dimensional structure is highly similar to that of a spider neurotoxin. 相似文献
4.
Dr. Thomas N. G. Handley Dr. Conan K. Wang Dr. Peta J. Harvey Dr. Nicole Lawrence Prof. David J. Craik 《Chembiochem : a European journal of chemical biology》2020,21(24):3463-3475
This review highlights the predominant role that NMR has had in determining the structures of cyclotides, a fascinating class of macrocyclic peptides found in plants. Cyclotides contain a cystine knot, a compact structural motif that is constrained by three disulfide bonds and able to resist chemical and biological degradation. Their resistance to proteolytic degradation has made cyclotides appealing as drug leads. Herein, we examine the developments that led to the identification and conclusive determination of the disulfide connectivity of cyclotides and describe in detail the structural features of exemplar cyclotides. We also review the role that X-ray crystallography has played in resolving cyclotide structures and describe how racemic crystallography opened up the possibility of obtaining previously inaccessible X-ray structures of cyclotides. 相似文献
5.
Ulf Göransson Dr. Anders Herrmann Dr. Robert Burman Linda M. Haugaard‐Jönsson K. Johan Rosengren Dr. 《Chembiochem : a European journal of chemical biology》2009,10(14):2354-2360
Cyclotides are a large family of plant peptides that are characterised by a head‐to‐tail circular backbone and three disulfide bonds that are arranged in a cystine knot. This unique structural feature, which is referred to as a cyclic cystine knot, gives the cyclotides remarkable stability against chemical and biological degradation. In addition to their natural function as insecticides for plant defence, the cyclotides have a range of bioactivities with pharmaceutical relevance, including cytotoxicity against cancer cell lines. A glutamic acid residue, aside from the invariable disulfide array, is the most conserved feature throughout the cyclotide family, and it has recently been shown to be crucial for biological activity. Here we have used solution‐state NMR spectroscopy to determine the three‐dimensional structures of the potent cytotoxic cyclotide cycloviolacin O2, and an inactive analogue in which this conserved glutamic acid has been methylated. The structures of the peptides show that the glutamic acid has a key structural role in coordinating a set of hydrogen bonds in native cycloviolacin O2; this interaction is disrupted in the methylated analogue. The proposed mechanism of action of cyclotides is membrane disruption and these results suggest that the glutamic acid is linked to cyclotide function by stabilising the structure to allow efficient aggregation in membranes, rather than in a direct interaction with a target receptor. 相似文献
6.
Antioxidant and Antithrombotic Activities of Rapeseed Peptides 总被引:2,自引:0,他引:2
Shao Bing Zhang Zhang Wang Shi Ying Xu 《Journal of the American Oil Chemists' Society》2008,85(6):521-527
The antioxidant and antithrombotic activities of crude rapeseed peptides (CRPs) and peptide fractions (RP25 and RP55) prepared
from aqueous enzymatic extraction (AEE) of rapeseed were determined. The reducing power of RP55 and CRPs was higher than that
of RP25 at the same concentrations. Rapeseed peptides exhibited marked antioxidant activities. The median effective dose (ED50) values of CRPs, RP25 and RP55 for α,α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging were 72, 499 and 41 μg/mL, respectively.
The ED50 values for RP25 and RP55 for hydroxyl radicals scavenging were 2.53 and 6.79 mg/mL, respectively while the ED50 values of RP55 and CRPs for inhibition of lipid peroxidation in a liposome model system were 4.06 and 4.69 mg/mL, respectively.
The inhibitory effect on lipid oxidation of RP55 was similar to that of ascorbic acid at a concentration of 5.0 mg/mL. A good
positive correlation existed between the peptide concentration and antioxidant activity. RP55 generally showed more potent
antioxidant activities except for hydroxyl radicals scavenging ability than RP25 and CRPs at the same concentrations, which
was thought to relate to the significantly higher contents of hydrophobic amino acid, tannin, and the brown color substances
in RP55. Rapeseed peptides possessed marked inhibitory activities on the thrombin-catalyzed coagulation of fibrinogen, however,
their inhibitory effects were not comparable to that of heparin. 相似文献
7.
Tamaoki H; Miura R; Kusunoki M; Kyogoku Y; Kobayashi Y; Moroder L 《Protein engineering, design & selection : PEDS》1998,11(8):649-659
To whom correspondence should be addressed Bioactive peptides of different
sources and biological functionalities, like endothelins, sarafotoxins, bee
and scorpion venom toxins, contain a consensus cystine framework,
Cys-(X)1-Cys/Cys-(X)3-Cys, which has been found to induce and stabilize a
homologous folding motif named the cystine- stabilized alpha-helix (CSH).
This is composed of an alpha-helical segment spanning the Cys-(X)3-Cys
sequence portion that is crosslinked by two disulfide bridges to the
sequence portion Cys-(X)1-Cys, itself folded in an extended beta-strand
type structure. Search for sequence homologies of peptides and proteins in
the SWISS-PROT and PDB data banks provided additional multiple examples of
this type of cystine framework in serine proteinase inhibitors, in insect
and plant defense proteins, as well as in members of the growth factor
family with the cystine-knot. A comparative analysis of the known
3D-structures of these peptides and proteins confirmed that the presence of
this peculiar cystine framework leads in all cases to a high degree of
local structural homology that consists of the CSH motif, except for the
cystine-knot, of the superfamily of the growth factors. In this case the
cyclic structure formed by the parallel cysteine connectivities of
Cys-(X)1-Cys/Cys-(X)3-Cys framework is penetrated by a third disulfide bond
with formation of a concatenated knot, and the two disulfide- bridged
peptide chains Cys-(X)1-Cys and Cys-(X)3-Cys are located in beta-strands.
Conversely, peptides and proteins containing Cys-(X)m- Cys/Cys-(X)n-Cys
cystine frameworks that differ from m/n = 1/3 were found to fold only
sporadically into local alpha-helical structures.
相似文献
8.
The Cyclic Cystine Ladder of Theta‐Defensins as a Stable,Bifunctional Scaffold: A Proof‐of‐Concept Study Using the Integrin‐Binding RGD Motif. 下载免费PDF全文
Anne C. Conibear Dr. Alexander Bochen Dr. K. Johan Rosengren Petar Stupar Dr. Conan Wang Prof. Dr. Horst Kessler Prof. Dr. David J. Craik 《Chembiochem : a European journal of chemical biology》2014,15(3):451-459
Peptides have the specificity and size required to target the protein–protein interactions involved in many diseases. Some cyclic peptides have been utilised as scaffolds for peptide drugs because of their stability; however, other cyclic peptide scaffolds remain to be explored. θ‐Defensins are cyclic peptides from mammals; they are characterised by a cyclic cystine ladder motif and have low haemolytic and cytotoxic activity. Here we demonstrate the potential of the cyclic cystine ladder as a scaffold for peptide drug design by introducing the integrin‐binding Arg‐Gly‐Asp (RGD) motif into the θ‐defensin RTD‐1. The most active analogue had an IC50 of 18 nM for the αvβ3 integrin as well as high serum stability, thus demonstrating that a desired bioactivity can be imparted to the cyclic cystine ladder. This study highlights how θ‐defensins can provide a stable and conformationally restrained scaffold for bioactive epitopes in a β‐strand or turn conformation. Furthermore, the symmetry of the cyclic cystine ladder presents the opportunity to design peptides with dual bioactive epitopes to increase activity and specificity. 相似文献
9.
Downstream Processes for Aqueous Enzymatic Extraction of Rapeseed Oil and Protein Hydrolysates 总被引:1,自引:2,他引:1
Shao Bing Zhang Zhang Wang Shi Ying Xu 《Journal of the American Oil Chemists' Society》2007,84(7):693-700
Downstream processes following aqueous enzymatic extraction (AEE) of rapeseed oil and protein hydrolysates were developed
to enhance the oil and protein yields as well as to purify the protein hydrolysates. The wet precipitate (meal residue) from
the AEE was washed with twofold water at 60 °C, pH 11 for 1 h. Emulsions from the AEE and the washing step were pooled and
submitted to a stepwise demulsification procedure consisting of storage-centrifugation and freezing–thawing followed by centrifugation.
Aqueous phases were pooled and adsorbed onto macroporous adsorption resins (MAR) to remove salts and sugars. Following extensive
rinsing with deionized water (pH 4), desorption was achieved by washing with 85% ethanol (v/v) to obtain crude rapeseed peptides
(CRPs). In a separate experiment, stepwise desorption was carried out with 25, 55, and 85% ethanol to separate the bitter
peptides from the other peptides. Using a combination of the AEE process, washing and demulsification steps, the yields of
the total free oil and protein hydrolysates were 88–90% and 94–97%, respectively. The protein recovery was 66.7% and the protein
content was enriched from 47.04 to 73.51% in the CRPs. No glucosinolates and phytic acid were detected in the CRPs. From the
stepwise desorption, a non-bitter fraction RP25 (containing 64–66% of total desorbed protein) had a bland color and significantly
higher protein content (81.04%) and hence was the more desirable product. 相似文献
10.
Michael Reinwarth Bernhard Glotzbach Michael Tomaszowski Sebastian Fabritz Dr. Olga Avrutina Prof. Dr. Harald Kolmar 《Chembiochem : a European journal of chemical biology》2013,14(1):137-146
Bioactive peptides often contain several disulfide bonds that provide the main contribution to conformational rigidity and structural, thermal, or biological stability. Among them, cystine‐knot peptides—commonly named “knottins”—make up a subclass with several thousand natural members. Hence, they are considered promising frameworks for peptide‐based pharmaceuticals. Although cystine‐knot peptides are available through chemical and recombinant synthetic routes, oxidative folding to afford the bioactive isomers still remains a crucial step. We therefore investigated the oxidative folding of ten protease‐inhibiting peptides from two knottin families, as well as that of an HIV entry inhibitor and of aprotinin, under two conventional sets of folding conditions and by a newly developed procedure. Kinetic studies identified folding conditions that resulted in correctly folded miniproteins with high rates of conversion even for highly hydrophobic and aggregation‐prone peptides in concentrated solutions. 相似文献
11.
Dr. Andrew Gould Prof. Dr. Julio A. Camarero 《Chembiochem : a European journal of chemical biology》2017,18(14):1350-1363
Cyclotides are globular microproteins with a unique head‐to‐tail cyclized backbone, stabilized by three disulfide bonds forming a cystine knot. This unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to chemical, thermal, and biological degradation compared to other peptides of similar size. In addition, cyclotides have been shown to be highly tolerant to sequence variability, aside from the conserved residues forming the cystine knot. Cyclotides can also cross cellular membranes and are able to modulate intracellular protein–protein interactions, both in vitro and in vivo. All of these features make cyclotides highly promising as leads or frameworks for the design of peptide‐based diagnostic and therapeutic tools. This article provides an overview on cyclotides and their applications as molecular imaging agents and peptide‐based therapeutics. 相似文献
12.
Plan MR Göransson U Clark RJ Daly NL Colgrave ML Craik DJ 《Chembiochem : a European journal of chemical biology》2007,8(9):1001-1011
The complete suite of cyclotides present in Oldenlandia affinis (Rubiaceae), the plant that was originally found to contain this unique family of circular proteins, has been characterised. This study expands the number of known cyclotides in this plant to 17, of which nine new sequences (kalata B9-B17) were characterised in this work. In addition, five derivatives that contain oxidation products of the conserved tryptophan were identified, and it was shown that the formation of these derivatives is catalysed by exposure to sunlight. Furthermore, we describe two "linear" cyclotide analogues. These acyclic peptides have three intact disulfide bonds, and their N and C termini coincide with the hypothesised cleavage sites from the precursor protein. This work increases our knowledge about the sequence variation that is accommodated by the cyclic cystine knot scaffold, confirms its applicability as a template for drug design, and also shows the first natural degradation pathways for cyclotides. These pathways have important implications for the persistence and environmental fate of the cyclotides if used as crop-protection agents. 相似文献
13.
RAYMOND S. ASQUITH PHILIP CARTHEW H. DIARMID HANNA MICHAEL S. OTTERBURN 《Coloration Technology》1974,90(10):357-367
The reactions with alkali of the disulphide bonds and the primary amino side–chains in wool have been investigated. Formation of dehydroalamine has been postulated and it has been conclusively identified in an alkali–treated, cystine–containing polypeptide. The mechanism of degradation of cystine in such a peptide has been further investigated and it has been shown that cysteine residues, produced from cystine during degradation, are also capable of degrading further to dehydroalanyl residues. The dehydroalanyl residues so produced are capable of reacting not only with other residues to form LAN and LAL, but also with other species present in the alkaline medium. The influence of amines on the cold setting of wool fibres with thioglycollates and on the dyeability of wool has been studied. Mechanisms are postulated to explain these effects. 相似文献
14.
Suzuki Masashi; Gerstein Mark; Johnson Tony 《Protein engineering, design & selection : PEDS》1993,6(6):565-574
The solution structure of one and two repeats of the SPKKDNA-binding motif is reported on the basis of NMR measurements.In dimethylsulphoxide (DMSO) the major population (approximately90%) of peptides, SPRKSPRK(S2) and GSPKKSPRK(S2b), adopts aconformation, which has two trans pralines. The two SP(R/K)Kunits hi these peptides are equivalent and each adopts a turnstructure exchanging with an extended structure. This is suggestedby an NOE connectivity of the /3-turn type, between the backboneamide protons of residues (j+2) and (j+3) and NOE connectivitiesof the Asx(a)-turn type, between protons of the tth Ser andthe backbone amide proton on residue (i+2). This suggests thateach SP(R/K)K unit has a structural intermediate between (ora combination of) a /3-turn and an Asx(a)-turn. In 90-10% DMSO/H2Oat 4C the two units of S2 are connected more tightly by foldinginto a short 3t0 helix, broken at the second proline. For anotherpeptide, Thr-Pro-Arg-Lys(Tl), the major population (75%) in100% DMSO comprises a /3-turn in rapid exchange with an extendedstructure. We did not observe an NOE connectivity of the Asx()type with the Tl peptide. A possible structure of the SPKK motifhi the complex with DNA is discussed. 相似文献
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16.
Oda M; Furukawa K; Ogata K; Sarai A; Ishii S; Nishimura Y; Nakamura H 《Protein engineering, design & selection : PEDS》1997,10(12):1407-1414
The individual repeats, R2 and R3, of the minimum specific DNA-binding
domain (R2R3) of c-Myb have very similar structures, with a helix-turn-
helix variation motif, although their sequence identity in the tandem
repeats is only 31%. From previous mutational and structural studies, the
third helices in both repeats were shown to directly recognize the specific
base sequence, PyAACG/TG. In order to elucidate the reason for the
imperfection of the tandem repeats at amino acid positions other than the
recognition helices, a series of R2R3 mutants was generated by swapping the
helices and the N-terminus in R2 to those in R3. Consequently, the sequence
composing the first helix of R2 was found to be essential for specific
DNA-binding, in addition to the third recognition helix of R2. Further
mutational studies revealed that the only indispensable residues in the
first helix are Val103 and Val1O7, which are involved in the hydrophobic
core of R2. These residues do not directly interact with the DNA, but they
contribute to the correct formation of helix 1 and the characteristic
packing of R2, which is slightly different from that of R3, and are
required for specific base recognition through strong cooperativity with
R3.
相似文献
17.
The extent to which cystine residues react when wool is steamed at temperatures above 10077deg;C was found to be very dependent on the pH of the wool and the temperature of the treatment, but was less sensitive to variations in the time of treatment. Extending the wool by up to 20% had no significant effect on cystine reactivity. Lanthionine was detected in the steamed wool in amounts which corresponded, approximately mole for mole, with the cystine losses recorded for the same samples, thus indicating that, under these conditions, even when the wool is at pH 3 0, almost all the cystine undergoing modification is converted to lanthionine. Measurements of the urea–bisulphite solubility of steamed wool provided indirect evidence of lanthionine formation. A new method of estimating lanthionine in protein hydrolysates, based on one–dimensional thin–layer chromatography combined with measurements of spot areas, is described. 相似文献
18.
Dr. Haifan Wu Arusha Acharyya Dr. Yibing Wu Dr. Lijun Liu Dr. Hyunil Jo Prof. Feng Gai Prof. William F. DeGrado 《Chembiochem : a European journal of chemical biology》2018,19(9):902-906
Although helices play key roles in peptide–protein and protein–protein interactions, the helical conformation is generally unstable for short peptides (10–15 residues) in aqueous solution in the absence of their binding partners. Thus, stabilizing the helical conformation of peptides can lead to increases in binding potency, specificity, and stability towards proteolytic degradation. Helices have been successfully stabilized by introducing side chain‐to‐side chain crosslinks within the central portion of the helix. However, this approach leaves the ends of the helix free, thus leading to fraying and exposure of the non‐hydrogen‐bonded amide groups to solvent. Here, we develop a “capped‐strapped” peptide strategy to stabilize helices by embedding the entire length of the helix within a macrocycle, which also includes a semirigid organic template as well as end‐capping interactions. We have designed a ten‐residue capped‐strapped helical peptide that behaves like a miniprotein, with a cooperative thermal unfolding transition and Tm≈70 °C, unprecedented for helical peptides of this length. The NMR structure determination confirmed the design, and X‐ray crystallography revealed a novel quaternary structure with implications for foldamer design. 相似文献
19.
Maoyuan Li Shifa Wang Huajing Gao Zijuan Yin Chaoli Chen Hua Yang Leiming Fang Jagadeesha Angadi Veerabhadrappa Zao Yi Dengfeng Li 《Journal of the American Ceramic Society》2023,106(4):2420-2442
A simple polyacrylamide gel method combined with low temperature sintering technology has been used to synthesize the C–O functional groups grafted MgAl2O4/C3N4/YMnO3 (MAO–CN–YMO) heterojunction photocatalysts with enhanced visible-light-induced photodegradation toward oxytetracycline hydrochloride (OTC-HCl). A variety of characterization methods are used to gain insight into the phase purity, crystal structure, microstructure, functional group information, elemental composition, surface defect, light response capability, and photocatalytic activity of the as-synthesized samples. The influences of the mass ratios of mCN/mYMO, mCN/mMAO, and mMAO/(mCN + mYMO) in CN–YMO, CN–MAO, and MAO–CN–YMO heterojunction photocatalysts on the photocatalytic activity for the degradation of OTC-HCl was also discussed, and the optimal mass ratio of mMAO/(mCN + mYMO) is identified as 15 wt%. The photocatalytic experiments confirmed that the MAO–CN–YMO heterojunction photocatalysts had high selectivity for the degradation of antibiotics. The prediction of the photocatalytic activity of the MAO–CN–YMO heterojunction photocatalysts for the degradation of OTC-HCl was made by a variety of intelligent algorithm models. The results of the whale optimization algorithm are highly consistent with the experimental results. Combined with the energy band theory and the characterization results of high-performance liquid chromatography–tandem mass spectrometry, the free radicals in the reaction solution preferentially attacked the –CH3, –NCH2, and –OH of OTC-HCl during the degradation of OTC-HCl by MAO–CN–YMO heterostructure photocatalysts, and then attack –C=O and –C=O–NH2, and finally perform ring-opening reaction to degrade OTC-HCl into nontoxic and harmless products of small molecules such as CO2, H2O, and NH4+. This work provides a new idea for the development of novel double p–n junction MAO–CN–YMO heterojunction photocatalysts for antibiotic degradation and the prediction of photocatalytic activity of multiple heterojunction photocatalysts by intelligent algorithms. 相似文献
20.
《Ceramics International》2019,45(14):17489-17494
Ultralight ceramics with striking mechanical properties and improved pore connectivity could have wide applications in areas ranging from catalyst support to hot gas filtration. However, creating such materials has proven to be a challenging target. This work demonstrated a novel methodology to prepare porous MgAl2O4 ceramics by calcining gelled MgO–Al2O3–SiO2 particle-stabilized foams. The striking green strength of dried foams can be achieved as a consequence of MgO hydration and subsequent formation of gelled Mg(OH)2 and MgO–SiO2–H2O skeleton. The decomposition of colloidal substance at elevated temperature resulted in the formation of small pores on the cell wall, thus forming the hierarchical porous architecture and improving the pore connectivity. The highly porous MgAl2O4 ceramics fired at 1600°C possessed the integrated properties of ultrahigh porosity (87.0%), improved pore connectivity and satisfactory compressive strength (7.93 MPa), showing great potential to be used in multiple industrial fields. 相似文献