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Abstract The neutral salt-soluble collagen which accumulates in the tissues of animals treated with penicillamine does not differ from normal in amino acid composition, specific optical rotation, and melting temperature. It has higher intrinsic viscosity, possibly due to a contamination with higher molecular weight aggregates originating from the depolymerization of insoluble collagen. In contrast to the aldehyde-deficient lathyritic collagen, the penicillamine collagen has an aldehyde content greater than normal and rapidly forms stable cross-links in vitro. Binding studies, involving film and equilibrium dialysis, revealed a significant interaction between collagen and compounds with a free α-aminothiol structure. The binding capacity of various collagens tested is proportional to their aldehyde content, and reduction with NaBH4 eliminates this interaction. Reduction of these aldehydes, amidination of the e-amino groups of lysine and hydroxylysine, or addition of sodium bisulfite (10-4 m) causes neutral salt-soluble collagen to behave like lathyritic collagen. It is postulated that the inhibition of cross-linking caused by penicillamine in vivo and in vitro involves a reversible interaction with the aldehydes present in tropocollagen to form a thiazolidine type complex, since compounds with adjacent free sulfhydryl and amino groups are necessary for activity. The solubilizing effect exhibited by α-amino-β-thiols on an incompletely cross-linked form of insoluble collagen as well as the generation of soluble collagen with a high aldehyde content can be attributed to the splitting of a Schiff's base intermediate. The structure which is responsible for the initial stabilization of the collagen fiber can be reduced with NaBH4, rendering the collagen insoluble in penicillamine.
Deshmukh et al. (Tue,) studied this question.