Peptides structure activity

To summarize, the picture that has emerged from these various studies of peptide structure-activity is as follows ... 

Jan-Christoph Westermann is a research officer at the Institute for Molecular Bioscience, The University of Queensland. He received his doctorate in chemistry from the Institute of Organic Chemistry at the University of Hamburg in 2006. He is working in the field of peptide structure-activity relationships and biomolecular NMR. 

S Hellberg, M Sjostrom, B Skagerberg, S Wold. Peptide quantitative structure-activity relationships, a multivariate approach. I Med Chem 30 1126-1135, 1987. 

While none of these neutrophil receptors has yet been sequenced, partial purification of the formyl peptide receptors has been reported (16). The formyl peptide receptor is particularly attractive because of the extensive structure-activity studies on peptide ligands by Freer and coworkers (17,18). The receptor is a trans-membrane glycoprotein with apparent molecular weight of 60,000 based on proteolysis (19) and photoaffinity (20) labeling studies. 

Fig. 1 Structure of BILN 2061 and initial lead peptide DDIVPC. Activities were determined in a radiometric assay against the NS3 protease domain...

Urotensin II Receptor (GPR14). The vasoactive cyclic peptide urotensin II (U-II) is the endogenous ligand of the G protein-coupled orphan receptor GPR14. Structure-activity relationships from 25 peptide analogs, which mobilize intracellular calcium in GPR14-transfected CHO cells, and the... 

This article summarises the general characteristics of a novel antibacterial target, peptide deformylase (PDF) and reviews the design, structure-activity relationships (SAR) and properties of known PDF inhibitors, including pre-clinical and clinical data for the most advanced members of this class. 

The first non-peptide oxytocin antagonists, based on a spiropiperidine template, were described by Merck in 1992 [68-70]. The binding affinity data for key compounds from this series are summarised in Table 7.2. The initial screening hit, L-342,643, (23), had modest (4/iM) affinity for rat uterine oxytocin receptors and very little vasopressin selectivity [71]. A structure activity relationship (SAR) study was carried out around this template, focussing on the toluenesulphonamide group. This work led to the identification of bulky lipophilic substitution as key to improved oxytocin potency, while the introduction of a carboxylic acid group led to improved... 

Several pathological self-polymerizing systems have been biophysi-cally characterized sufficiently to permit identification of protein or peptide species that could serve as molecular targets in a structure-activity relationship. These include transthyretin (TTR) [73-76], serum amyloid A protein (SAA) [77], microtubule-associated protein tau [78-80], amylin or islet amyloid polypeptide (IAPP) [81,82], IgG light chain amyloidosis (AL) [83-85], polyglutamine diseases [9,86], a-synuclein [47,48] and the Alzheimer s (3 peptide [87-96]. A variety of A(3 peptide assay systems have been established at Parke-Davis to search for inhibitors of fibril formation that could be therapeutically useful [97]. 

Hellberg, S., Eriksson, L., Jonsson, J., Lindgren, F., Sjostrom, M., Skagerberg, B., Wold, S. and Andrews, P. (1991), Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships , Int.J. Peptide Protein Res., 37, 414-424. 

Bowman, J.W., Friedman, A.R., Thompson, D.P., Ichhpurani, A.K., Kellman, M.F. and Geary, T.G. (1996) Structure-activity relationships in a nematode FMRFamide-like peptide, KNEFIRFamide. Peptides 17, 381-387. 

It is the sequence and types of amino acids and the way that they are folded that provides protein molecules with specific structure, activity, and function. Ionic charge, hydrogen bonding capability, and hydrophobicity are the major determinants for the resultant three-dimensional structure of protein molecules. The a-chain is twisted, folded, and formed into globular structures, a-helicies, and P-sheets based upon the side-chain amino acid sequence and weak intramolecular interactions such as hydrogen bonding between different parts of the peptide... 

Zelezetsky I, Tossi A (2006) Alpha-helical antimicrobial peptides - using a sequence template to guide structure-activity relationship studies. BBA-Biomembranes 1758 1436-1449... 

---