Action of [1,6-Di-alanine]-oxytocin and [1,6-Di-serine]-oxytocin on the rat uterus and mammary gland in vitro

Poláček, Ivo; Krejcí, I; Nesvadba, H.; Rudinger, J.

doi:10.1016/0014-2999(70)90306-7

Cited by 13 publications

(7 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yet without the stabilizing effect of the bridge element the probability of obtaining this conformation out of all the other possible ones is very low. This is in agreement with the very low activity found (Polacek et al, 1970).…”

Section: Discussionsupporting

confidence: 92%

“…The biological activities of oxytocin are intimately connected with the intramolecular ring size and especially with its geometry (Rudinger, 1971): An open-chain derivative ( Polacek et al, 1970). However, small changes in the spatial arrangement of the disulfide bond induced by replacement of one sulfur atom by methylene group in position 1 or 6 in desamino-"carba"-oxytocin analogs (Jost and Sorm, 1971a,b), or of both sulfur atoms of the bridge by methylene group in desamino-"dicarba"-oxytocin (Jost and Rudinger, 1967) has given rather biologically potent analogs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Role of the internal cross-link in oxytocin. Preparation of mercury mercaptide oxytocin derivatives

Sperling¹,

Gorecki²

1974

Biochemistry

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Role of the internal cross-link in oxytocin. Preparation of mercury mercaptide oxytocin derivatives

Sperling¹,

Gorecki²

1974

Biochemistry

View full text Add to dashboard Cite

“…In a third example, ArgVP and oxytocin are compared with [1, and [1,6-dialanine]-oxytocin; the latter has been particularly thoroughly studied for some of its biological activities (9). Although the conformational constraint usually imposed by the disulfide bridge is removed entirely in these acyclic analogs, they retain exceedingly low, but definite, biological activities, e.g.…”

Section: Modifications Of Type Amentioning

confidence: 99%

Relation of the Conformation of Oxytocin to the Biology of Neurohypophyseal Hormones

Walter¹,

Schwartz²,

Darnell³

et al. 1971

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The conformation of oxytocin is related to the evolution and to some of the biological activities of neurohypophyseal hormonal peptides. On the basis of the three-dimensional structure, positions 3, 4, 7, and 8 are the only loci at which naturally occurring neurohypophyseal peptides may be expected to differ. The side chains of these amino-acid residues are the primary determinants of the differential specificity in interactions between neurohypophyseal hormones and their receptors.There are three general groups of structural modifications of neurohypophyseal hormones which can be correlated with specific changes in biological activity: (a) those affecting the stabilization of the backbone of the peptide, which would extensively perturb the spatial relationships among all the constituent amino acids and hence, affect both affinity and intrinsic activities uniformly; (b) those which, while retaining the stability of the backbone conformation, alter the steric environment and charge distribution of limited surface areas, and thereby can affect affinity and intrinsic activity differentially; and (c) those changing the steric and electronic requirements of moieties comprising the active surface of the neurohypophyseal peptide, without perturbing the peptide backbone of the hormone molecule and, hence, affecting intrinsic activity without altering affinity.Neurohypophyseal hormones exhibit a variety of biological effects on contractile and membrane-transport phenomena. The initial event in the action of any hormone on its target cell, quite independent of any intermediary events and of the nature of the final response, requires a high degree of topological and chemical complementarity of the hormonal molecule and some macromolecular receptor. The elucidation of the peptide backbone of oxytocin as two a-turns (1) has afforded us a point of departure for a consideration of how the conformation of oxytocin can be related to the evolution of neurohypophyseal hormones and, in addition, of how the differential biological properties of naturally occurring neurohypophyseal peptides and their synthetic congeners can be envisioned.The latter approach assumes that the "information" contained in the hormonal peptide finds full expression in the biological parameter measured. Expressed in terms of current receptor theory (2), a "stimulus", generated as a consequence of a hormone interacting with its specific target-tissue discriminator, depends upon three factors: (a) hormone concentration, (b) hormone affinity, i.e., the ability of the hormone to bind to its receptor, (c) hormone effectiveness, i.e., Abbreviation: ArgVP, arginine vasopressin. the ability to generate a stimulus at optimal receptor occupation (intrinsic activity). While the affinity parameter can usually be readily approximated experimentally, this cannot be said of intrinsic activity-neither for in vivo situations nor for in vitro situations. In fact, we postulate that all peptide hormones which initiate processes involving one or more coupling steps prio...

show abstract

“…Anal. Z-Gln-Asn-JDpr(Boc)-Pro-Leu-Gly-NH2 (3). The Z group was cleaved from 2 (3 g, 4.1 mmol) as described above.…”

Section: Methodsmentioning

confidence: 99%

“…This point is dramatically illustrated by the nearly total lack of biological activity observed for the acyclic analogues, [Ala1,6]oxytocin, 3 [Ala1,6]arginine-vasopressin, 4 and [Ser1,6]oxytocin. 3 The fact that the reactivity of the disulfide is not required for biological activity is amply demonstrated by the significant biological activities possessed by oxytocin analogues in which the 20-membered ring has been preserved, but one sulfur atom replaced by a methylene group5™11 or both sulfur atoms by an ethylene group.6,9,11™15 Changes of the dihedral angle of the bridging group exercise such a profound influence on the overall conformational integrity of the molecule that even a minor modification such as substitution of either one or both sulfur atoms by selenium evokes a definite change in the spectrum of biological activities.16'18 A displacement of the disulfide bond within the four-atom bridge as in [1mercaptoacetic acid,6-homocysteine]oxytocin19 also dramatically alters the activities.…”

mentioning

confidence: 99%

Replacement of the disulfide bond in oxytocin by an amide group. Synthesis and some biological properties of [cyclo-(1-L-aspartic acid, 6-L-.alpha.,.beta.-diaminopropionic acid)]oxytocin

Smith¹,

Walter²,

Moore³

et al. 1978

J. Med. Chem.

View full text Add to dashboard Cite

As part of a continuing investigation of the steric and electronic functions of the disulfide group in neurohypophyseal hormones on their biological activity, the synthesis of "oxytocin lactam", [cyclo-(1-aspartic acid,6-alpha,beta-diaminopropionic acid)]oxytocin, has been undertaken. The protected nonapeptide was prepared in a stepwise manner by solution techniques; after removal of side-chain protecting groups, formation of the briding amide bonds was accomplished by oxidation-reduction condensation. The analogue possesses rat uterotonic, avian vasodepressor, and rat antidiuretic potencies of 16 +/- 2, 6.6 +/- 0.6, and 5.6 +/- 3.8 units/mg, respectively.

show abstract

Action of [1,6-Di-alanine]-oxytocin and [1,6-Di-serine]-oxytocin on the rat uterus and mammary gland in vitro

Cited by 13 publications

References 14 publications

Role of the internal cross-link in oxytocin. Preparation of mercury mercaptide oxytocin derivatives

Role of the internal cross-link in oxytocin. Preparation of mercury mercaptide oxytocin derivatives

Relation of the Conformation of Oxytocin to the Biology of Neurohypophyseal Hormones

Replacement of the disulfide bond in oxytocin by an amide group. Synthesis and some biological properties of [cyclo-(1-L-aspartic acid, 6-L-.alpha.,.beta.-diaminopropionic acid)]oxytocin

Contact Info

Product

Resources

About