ABSTRACT
The hinge structure, also known as hinge region or bend, is a special structure found in some antimicrobial peptides. Most studies on antimicrobial peptides focused on the standard secondary structure of α-helix and β-sheet, while the hinge structure and its functions were rarely studied. The hinge structure confers the antimicrobial peptides an improved structural flexibility, which may promote their disruptive effect on bacterial membrane or their binding efficiency to the intracellular targets, thus resulting in a higher antibacterial activity. Meanwhile, the hinge structure may reduce the structural rigidity, which may eliminate the cytotoxicity of antimicrobial peptides to eukaryotic cells. This article reviews the structural characteristics of the hinge structure, its effects on the biological activity of antimicrobial peptides and application in the molecular design, with the aim to provide a reference for the design and development of new antimicrobial peptides.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Pore Forming Cytotoxic Proteins , Protein Structure, SecondaryABSTRACT
Cathelicidins play critical roles in mammalian innate immune defense against invasive bacterial infection. In addition to their broad-spectrum bactericidal effect, cathelicidins are interesting peptide-based drug templates because they have multiple functions including anti-inflammatory, wound healing, and angiogenesis promotion. This article summarizes the aim and method of cathelicidin molecular designs. Residue mutation, fragment assembly, chemical modification, and construction of conjugates and dimers are usually used to increase the biological activities. Addition or deletion of certain residues, disruption of leucine zipper and phenylalanine zipper are used to reduce the hemolysis and cytotoxicity. By substituting L-amino acids with D-amino acids, circular constructions and immobilization, cathelicidins' in vitro and in vivo stability could be greatly enhanced, especially their proteinase resistance.
ABSTRACT
Antimicrobial peptides ( AMPs) are a kind of micromolecular peptides with antibacterial , antivirus and anti-tumor activities.Unlike conventional antibiotics , acquisition of resistance by a sensitive microbial strain against AMPs is surprisingly improbable .AMPs are not widely used clinically due to their toxicity , susceptibility to proteolysis and high manufacturing cost .Researchers have obtained some AMPs with high activity and low toxicity by structure modifications . The molecular design of AMPs as well as their development in the future are reviewed .
ABSTRACT
HIV-1 protease inhibitors play a very important role in AIDS chemotherapy, but with the rapid emergence of drug resistance as a result of the residue mutation of HIV-1 protease, developing effective protease inhibitors with superior activity against drug-resistant variants is becoming the research hotspot in AIDS drug design. Meanwhile, some molecular designing strategies of anti-drug-resistant HIV-1 protease inhibitors were put forward and applied to develop anti-AIDS drugs. The purpose of the research is introducing these molecular designing strategies to develop potent HIV-1 protease inhibitors to combat drug resistance, including substrate envelope hypothesis, strengthening the binding of inhibitors to HIV-1 protease and searching inhibitors acting in novel sites of HIV-1 protease.
ABSTRACT
In response to problems from the development of multi-drug-resistant pathogenic bacteria,it is urgent to find new antimicrobials.Antimicrobial peptides(AMPs) are a kind of ideal new antimicrobials with the advantages including their potential for broad-spectrum activity,rapid bactericidal activity and low propensity for resistance development,and have a bright future.Alpha-helical antimicrobial peptides are a main kind of AMPs.The following features was reviewed and elucidated including the structure and activity relationship(SAR) from different aspects including the degree of helicity,hydrophobic moment,hydrophobicity,net positive charges and so on,and the application of SAR on the molecular design and improvement of AMPs.
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Objective To explore how to trigger an HLA Ⅰ restricted CD8 + T cell response to exogenously synthesized peptides in vitro . Methods A new panel of therapeutic peptides based on the immunodominant B and CTL epitopes of HBV PreS 2 region and HBcAg and the tetanus toxoid common T helper epitopes were synthesized by Merrifield solid phase peptide synthesis, and HLA A2 + human PBMCs were used to investigate the immunological properties of the mimetic peptides. Results The results demonstrated that the peptides could trigger vigorous CD8 + HBV specific CTL responses in vitro specifically and effectively. Conclusion The results reveal that T helper plus B epitopes designing with the introduction of short and flexible linker can remarkably improve the immunogenicity of short peptides and hence produce effective CTL responses in vitro .
ABSTRACT
Objective:To discover some high hydrophilic profiles of the human C5a anaphylatoxin based on relationship between the structure and function of the protein and the protein molecular design principles.Methods:The peptides were synthesized by 431A automatic peptide synthesizer,purified by PHLC and confirmed by caplilliary electrophoresis.Results:The N terminus No.9 30 profile of the C5aR(P22) could interacte with anti C5aR McAb(S5/1,from Serotic Co.),as determined by ELISA.Furthermore,it could be inhibited OD490 values remarkably by 10.0 ?g/L rhC5a(P
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Objective To obtain a potent bacterial DNA antagonizing CpG oligonucleotides (CpG-N ODN) from the structures of Adv2, 5 DNA. Methods Ten putative CpG-N ODNs were synthesized and investigated. Their abilities to inhibit the TNF-? release from hPBMC were observed. Based on the above results, the putative CpG-N ODN was redesigned according to the relationship between the structure and free energy using RNA structure software (version 3.71). Eleven putative CpG-N ODNs were synthesized and screened. Results Out of the ten initial CpG ODNs, ODN101 was the only CpG-N ODN with weak activity to inhibit TNF-? release from hPBMC induced by CpG-N ODN. After redesign, five CpG-N ODNs with strong activity were confirmed. Conclusion Six CpG-N ODNs were obtained with activity to inhibit TNF-? release from hPBMC induced by CpG-N ODN.