ALTERATION IN THE CONFORMATIONAL STABILITY OF COLLAGEN CAUSED BY THE INCORPORATION OF THE LYSINE ANALOG S-2-AMINOETHYLCYSTEINE

We studied the effects of the lysine analogue S-2-aminoethylcysteine o n the activation of lysyl tRNA and on the secretion and conformational stability of newly synthesized type I collagen in embryonic chick ten don fibroblasts. The analogue competed efficiently with lysine for act ivation onto tRNA without affecting significantly the activation of ot her amino acids (K-m for lysine: 1.6 mu M; K-i for S-2-aminoethylcyste ine: 1.4 mu M). The analogue also profoundly inhibited the synthesis a nd secretion of [C-14]procollagen but did not affect the synthesis or secretion of non-collagenous proteins. Although the [C-14]proline-labe led procollagen synthesized in the presence of S-2-aminoethylcysteine contained normal levels of hydroxyproline, it was susceptible to diges tion with pepsin at 25 degrees C, indicating that incorporation of the analogue altered the conformational stability of the collagen triple helix. This analogue should be a powerful tool to further study the ro le of lysine on collagen structure and to determine how altered collag en structure affects its synthesis and secretion. Furthermore, this an alogue may be a potent and selective inhibitor of collagen accumulatio n in pathologic conditions accompanied by tissue fibrosis.