A comparative study of the proton and carbon-13 nuclear magnetic resonance spectral parameters of the peptide hormone oxytocin and of its competitive inhibitor [1-L-penicillamineloxytocin has been made, and the results analyzed in terms of comparative conformational and dynamic properties. The results indicate that oxytocin has a flexible conformation, while [1-L-penicillamineJoxytocin has a more restricted conformation. The results provide a framework for understanding the mechanism of peptide hormone agonism and antagonism for these compounds, and an approach for understanding some features of the interaction of the hormone and related compounds with their receptor. Nuclear magnetic resonance (NMR) spectroscopy has been widely used to investigate the three-dimensional structure of small peptides in solution (1). The mean conformation obtained is generally an average of a manifold of conformations, and the question arises of the application of these findings to the biological activity for these compounds. Even if the hypothesis that the native conformation of a protein is the one of lowest free energy (2) is accepted, this cannot necessarily be extrapolated to the case of small peptides with biological activity (3, 4). From NMR and other conformational studies, information regarding the biologically active conformation(s) cannot generally be obtained in an absolute manner unless the following conditions can be met: (a) the peptide is flexible in solution and criteria can be established for a direct unequivocal relationship between the mean conformation in solution and that adapted by the hormone at the receptor, or (b) the conformation is so rigid that we can assume it will not be significantly modified by interaction with the receptor.The problem encountered in (a) is extremely complicated because we have very little knowledge of hormone receptors, of peptide hormone interactions with receptors, or of the physical-chemical basis for the mechanism of hormone action. Nonetheless some approaches have been suggested (ref. 5 and refs. therein) to define the relationship mentioned in (a). To our knowledge, the situation under point (b) has never been demonstrated experimentally for small peptide hormones. It was suggested some time ago (6), and there is increasing evidence (1, 7-9) that small peptide hormones do not have a rigid solution conformation.In this paper, we report on a comparative conformational study of the peptide hormone oxytocin, Cys-Tyr-Ile-Gln-Asnys-Pro-Leu-Gly-NH2, and [1-L-penicillaminejoxytocin, §I C(CH3)2CH(NH2)CO-Tyr-IIe-G.n-Asn-C5ys-Pro-Leu-Gly-NH2 ([Penl'oxytocin), a competitive inhibitor of oxytocin (ref. 10 and refs. therein), in aqueous solution. From these studies we suggest that the conformational flexibility of oxytocin is an important property for its agonist activity at the receptor, and that the antagonist activity of [Penl]oxytocin is related to its relative coformational rigidity. We also briefly discuss the effect of relative rigidity on the binding kinetics of the ant...

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Dow and Rosen’s work in 1965 formed an intellectual framework for compressive strength of unidirectional composites. Compressive strength was explained in terms of micro-buckling, in which filaments are beams on an elastic foundation. While groundbreaking, the discrepancy between model predictions and observed compressive strength is well known. This study builds on Dow and Rosen’s model specifically with respect to the dominant shear mode instability. A new method that accounts for matrix thermal residual strain, matrix compressive and shear stresses, with associated reductions in tangent modulus due to matrix non-linearity, is proposed. The method is validated using a specific test case, which is conducted to precisely account for microscopic fiber alignment and matrix non-linearity. Accordingly, a method of measuring and accounting for a continuum of fiber misalignment is developed. Predictions are compared to literature values, with variations in fiber modulus, matrix modulus, and volume fraction. Good agreement is shown, both in terms of trend and magnitude. The approach successfully preserves initial in-plane shear stiffness, while showing that in-plane shear stiffness decreases significantly as compressive stress increases.

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92, 5170 (1970).(2) Throughout this paper MH+ designates the protonated amino acid, while (MH+ -X) designates the ion resulting from the loss of X from the protonated molecule.(3) P.