Conformational and dynamic considerations in peptide structure-function studies

Victor J Hruby, Henry I. Mosberg

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Most small peptide hormones and neurotransmitters are highly flexible, conformationally labile molecules in aqueous and other environments. Thus efforts to determine the relationships between conformational properties of these peptides in aqueous and other solvents and their biological activities at membrane receptors have been difficult and of limited success. One approach which may provide a more rational basis for conformation-activity relationships is the design of conformationally restricted, semi-rigid analogs of the native peptides which still possess high potency and/or antagonist properties. In addition to the increased likelihood that the conformational properties determined for these derivatives in aqueous or other solvent environments will have biological relevance, such analogs are likely to have higher specificity for particular receptors, greater in vivo stability, and perhaps even oral activity. The application of this approach to the design of highly potent oxytocin antagonists is discussed with particular emphasis on the conformational and dynamic properties which appear to differentiate agonist and antagonist analogs. The results of these studies are briefly compared with similar studies with somatostatin, angiotensin, bradykinin, α-melanotropin and enkephalin, and discussed in terms of likely further developments.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalPeptides
Volume3
Issue number3
DOIs
StatePublished - 1982

Fingerprint

Melanocyte-Stimulating Hormones
Peptides
Peptide Hormones
Enkephalins
Angiotensins
Bradykinin
Oxytocin
Bioactivity
Somatostatin
Neurotransmitter Agents
Conformations
Derivatives
Membranes
Molecules

Keywords

  • Conformation-activity
  • Hormone antagonists
  • Nuclear magnetic resonance
  • Oxytocin
  • Peptide hormones
  • Peptide neurotransmitters

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Conformational and dynamic considerations in peptide structure-function studies. / Hruby, Victor J; Mosberg, Henry I.

In: Peptides, Vol. 3, No. 3, 1982, p. 329-336.

Research output: Contribution to journalArticle

@article{d0b43cef1416439196a7af3e9369e2c3,
title = "Conformational and dynamic considerations in peptide structure-function studies",
abstract = "Most small peptide hormones and neurotransmitters are highly flexible, conformationally labile molecules in aqueous and other environments. Thus efforts to determine the relationships between conformational properties of these peptides in aqueous and other solvents and their biological activities at membrane receptors have been difficult and of limited success. One approach which may provide a more rational basis for conformation-activity relationships is the design of conformationally restricted, semi-rigid analogs of the native peptides which still possess high potency and/or antagonist properties. In addition to the increased likelihood that the conformational properties determined for these derivatives in aqueous or other solvent environments will have biological relevance, such analogs are likely to have higher specificity for particular receptors, greater in vivo stability, and perhaps even oral activity. The application of this approach to the design of highly potent oxytocin antagonists is discussed with particular emphasis on the conformational and dynamic properties which appear to differentiate agonist and antagonist analogs. The results of these studies are briefly compared with similar studies with somatostatin, angiotensin, bradykinin, α-melanotropin and enkephalin, and discussed in terms of likely further developments.",
keywords = "Conformation-activity, Hormone antagonists, Nuclear magnetic resonance, Oxytocin, Peptide hormones, Peptide neurotransmitters",
author = "Hruby, {Victor J} and Mosberg, {Henry I.}",
year = "1982",
doi = "10.1016/0196-9781(82)90095-X",
language = "English (US)",
volume = "3",
pages = "329--336",
journal = "Peptides",
issn = "0196-9781",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Conformational and dynamic considerations in peptide structure-function studies

AU - Hruby, Victor J

AU - Mosberg, Henry I.

PY - 1982

Y1 - 1982

N2 - Most small peptide hormones and neurotransmitters are highly flexible, conformationally labile molecules in aqueous and other environments. Thus efforts to determine the relationships between conformational properties of these peptides in aqueous and other solvents and their biological activities at membrane receptors have been difficult and of limited success. One approach which may provide a more rational basis for conformation-activity relationships is the design of conformationally restricted, semi-rigid analogs of the native peptides which still possess high potency and/or antagonist properties. In addition to the increased likelihood that the conformational properties determined for these derivatives in aqueous or other solvent environments will have biological relevance, such analogs are likely to have higher specificity for particular receptors, greater in vivo stability, and perhaps even oral activity. The application of this approach to the design of highly potent oxytocin antagonists is discussed with particular emphasis on the conformational and dynamic properties which appear to differentiate agonist and antagonist analogs. The results of these studies are briefly compared with similar studies with somatostatin, angiotensin, bradykinin, α-melanotropin and enkephalin, and discussed in terms of likely further developments.

AB - Most small peptide hormones and neurotransmitters are highly flexible, conformationally labile molecules in aqueous and other environments. Thus efforts to determine the relationships between conformational properties of these peptides in aqueous and other solvents and their biological activities at membrane receptors have been difficult and of limited success. One approach which may provide a more rational basis for conformation-activity relationships is the design of conformationally restricted, semi-rigid analogs of the native peptides which still possess high potency and/or antagonist properties. In addition to the increased likelihood that the conformational properties determined for these derivatives in aqueous or other solvent environments will have biological relevance, such analogs are likely to have higher specificity for particular receptors, greater in vivo stability, and perhaps even oral activity. The application of this approach to the design of highly potent oxytocin antagonists is discussed with particular emphasis on the conformational and dynamic properties which appear to differentiate agonist and antagonist analogs. The results of these studies are briefly compared with similar studies with somatostatin, angiotensin, bradykinin, α-melanotropin and enkephalin, and discussed in terms of likely further developments.

KW - Conformation-activity

KW - Hormone antagonists

KW - Nuclear magnetic resonance

KW - Oxytocin

KW - Peptide hormones

KW - Peptide neurotransmitters

UR - http://www.scopus.com/inward/record.url?scp=0019973142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019973142&partnerID=8YFLogxK

U2 - 10.1016/0196-9781(82)90095-X

DO - 10.1016/0196-9781(82)90095-X

M3 - Article

VL - 3

SP - 329

EP - 336

JO - Peptides

JF - Peptides

SN - 0196-9781

IS - 3

ER -