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THE UNIVERSITY OF MANITOBA STUDIES ON OVINE PLACINTAL ...

THE UNIVERSITY OF MANITOBA STUDIES ON OVINE PLACINTAL ...

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-23-<br />

growth-promoting ef,fect, whereas cleavage of only one bond<br />

did not Lead to any loss of activity. Símilarly, Neri et<br />

aI (1972) observed a reduction of Lactogenic activity in the<br />

pigeon crop-sac assay onJ-y when both disulfide bonds of hpL<br />

were cleaved. Aubert et al (1974) have observed a good<br />

correlation between rnolecular conformation of hpl and its<br />

biotogic activíty vrhen they used derivaÈives that still<br />

contained the ent,ire primary structure but had undergone<br />

some chemical modif icat,iont toss of tertiary structure was<br />

accompanied by J.oss of activity. However, these results<br />

conflict vrith those of another group (Aloj et al, 1972;<br />

Handwerger et al , 1972; Sherwood et al , Lg72r, vrho selectively<br />

disrupted the disulfide bonds, simultaneously destroying<br />

a methionine and a síngle tryptophan. residue, and found that<br />

this treatment did noÈ affect the 1actogenic activity of<br />

hPI,. Hovrever, it,s immunological potency was considerably<br />

di¡ninished. These investigators concluded that, since the<br />

three-dimensional structure of hpI, did not appear to be<br />

necessary for its lactogenic activity, this effect must<br />

reside in a small portion of the polypeptide chain. In support<br />

of this hypothesis, they found that çy¡¡6q¿¡ bromide trêatment or pérfor;nic<br />

acid digest of hpl retained lactogenic activity. Other studies<br />

in which hPL has been enzymatically cleaved also suggest that.<br />

partial hydrolysis of the hormone does not destroy its<br />

biological activity. Neri et al (I9?2) denonstrateil that<br />

tryptic digestion of four hpl. bonds leads to only 30t loss<br />

of lactogenic actiyity and no reduction in somatotropic activity.

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