Structure-Activity Relationships of Kinins

摘要: The elucidation of the structure bradykinin by Elliott et al. (1960) and kallidin Werle (1961) independently Pierce Webster (1961), as well synthesis these two naturally occurring polypeptides Boissonnas (1960; cf. Guttmann al., 1962), Pless (1962), Nicolaides colleagues stimulated subsequent intensive research work. use larger amounts synthetic material made an exact quantitative determination various pharmacological effects possible, such action on smooth muscles in vitro extravasai vivo, bronchoconstriction, heart vascular system, influence renal blood flow, stomach secretion, pain sensation, leukocyte emigration. large number biological that can be demonstrated extremely low doses raised many questions about importance kinins physiological pathological processes (Sturmer, 1966; Wiegershaiisen Paegelow, Erdos, Werle, 1967; Habermann, 1968). Peptide chemists already engaged with modifications natural molecules became interested clarifying following problems: Which chemically functional or nonfunctional groups are essential for activity, what special structural requirements responsible attachment to a hypothetical receptor ? Related this is search specific inhibitors bradykinin, which could decisive investigations participation mediator substances physiological-pathological processes. A further goal chemist differentiate activities, i.e. reduce unpleasant side minimum chemical prolong most interesting only short duration when original molecule applied. An improvement kind possible if peptide modified way vivo enzymatic degradation chain blocked without destruction active centers molecule.