Structure-activity relationships peptide analogues

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. 

Amino-acid abbreviations are spelled out in Appendix V. Through a series of structure-activity relationship studies, the bioactive conformation and peptide sequences that produce undesirable biologic responses were identihed. Also identified were sequences susceptible to proteolysis, and a working-model compound that eliminated these sequences was proposed (Figure 4.6). This allowed the rational design of optimized somatostatin analogues with desirable biologic characteristics and activity and increased stability. 

The first total synthesis of a phallotoxin was that of norphalloin, the norvaline analogue of phalloidin.16 This synthesis, outlined in Scheme 2, initially involves the synthesis of two building blocks followed by their covalent binding via a tryptathionine moiety. Subsequent deprotection and coupling steps using classical methods of peptide synthesis results in the formation of norphalloin, which has proved to be even more toxic than the natural toxins. Since the synthesis of norphalloin, a number of synthetic analogues have been synthesized in order to obtain information on structure-activity relationships.[7 8]... 

Collantes, E.R. and Dunn III, W.J. (1995). Amino Acid Side Chain Descriptors for Quantitative Structure-Activity Relationship Studies of Peptide Analogues. J.Med.Chem.,38,2705-2713. 

Levesque. L. etai (1991) The interaction of 3.5-pyrazolidinedione drugs with receptors for f-Met-Leu-Phe on human neutrophil leukocytes a study of the structure- activity relationship. Can. J. Physiol. Pharmacol., 69,419-425. Levesque. L. era (1992) Comparison of two classes of non-peptide drugs as antagonists of neutrophil receptors for f-Met-Leu-Phe. Pyrazolons and iodinated radiographic contrast agents. Biochem. Pharmacol., 43. 553-560. Derian. C.K. er at (1996) Selective inhibition of N-formylpeptide-induced neutrophil activation by carbamate-modified peptide analogues. Biochemistry, 35.1265-1269. 

Collantes, E.R. and Dunn, W.J. Ill (1995) Amino acid side chain descriptors for quantitative structure-activity relationship studies of peptide analogues. /. Med. Chem., 38. 2705-2713. 

Beck-Sickinger, A.G., Jung, G., Gaida, W., Koppen, H. Schnorrenberg, G. (1990a) Structure-activity relationships of c-terminal neuropeptide Y peptide segments and analogues composed of sequence 1-4 linked to 25-36. Eur.J. Biochem. 194, 449—456. 

The bioactive conformation is consistent with the farmacoforic points that are identified through structure activity relationship studies (SAR). SAR studies include the synthesis of many peptide and/or non peptide analogues displaying selectivity for one or another of the receptors and their pharmacologically defined subtypes [19] such as delta 1- and delta2-opioid receprtor subtypes [20]. 

Fischer, P. M., Zhelev, N. Z., Wang, S., Melville, J. E., Fahraeus, R., Lane, D. P. (2000). Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector Penetratin. Journal of Peptide Research, 55, 163-172. 

Human adrenocorticotrophin (ACTH), a peptide hormone consisting of 39 amino acid residues (Fig. 5.3a) was identified as an important factor of the hypothalamus-pituitary-adrenal system in the 1950s, and numerous studies have been conducted ever since to elucidate its struc-ture, plasma concentrations, structure-activity relationships, degradation products, and synthetic analogues.ACTH was shown to... 

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