Cyclic Melanotropins, Part Vi*. Reverse Phase Hplc Studies

The chromatographic behavior of 17 cyclic [Cys, Cys]-a-melanocyte stimulating hormone (a-MSH, a-melanotropin) analogs were studied on two reversed phase columns (Altech and Vydac) using several mobile phases. It was observed that analogs which contain a D-amino acid were always eluted earlier than the corresponding L-amino acid-containing analogues. Substitution of penicillamine for cysteine in the 4 position led to a more lipophilic compound as expected, but when penicillamine was substituted in the 10 position, apparently a less lipophilic compound resulted. These observations can be interpreted as a result of a conformational change in the molecule caused by the particular substitution. Furthermore, decreasing the size of the intramolecular disulfide ring led to a decrease in lipophilicity (i.e. retention time). The carba modification of the disulfide bridge had a similar effect as previously seen in oxytocin and vasopressin, that is, a decrease in retention time.