The resistance of crosslinked insulin derivatives to pepsin and trypsin.

The introduction of a crosslink between the amino groups of A1-glycine and B29-lysine of the insulin molecule leads to a marked decrease in sensitivity towards pepsin. Under conditions where insulin is completely degraded over 70% of N alpha A1, N epsilon B29-(carbonyl-bis-methionyl) insulin [OC(Met)2] remain intact. The resistance increases with the length of the crosslink, i.e. oxalyl less than OC(Met)2 less than dodecanedioyl insulin. The carbonyl-bis-methionyl derivative is also stabilized against tryptic attack, but to a smaller degree.