DIURETIC ACTIVITY OF C-TERMINAL GROUP ANALOGS OF THE INSECT KININS INACHETA-DOMESTICUS

A series of insect kinin analogues, AFFPWG-X, modified at the C-termin al group, were evaluated in a cricket Malpighian tubule secretion bioa ssay. The results were compared with activity profiles observed in a c ockroach hindgut myotropic bioassay for these analogues. Although the replacement of the C-terminal amide group with a negatively charged ac id leads to a precipitous drop in diuretic activity, it can be partial ly restored with the introduction of ester groups such as methyl or be nzyl. The presence of branched chain character in the C-terminal group or a C-terminal alpha-carbon-amide distance spanning five methylene g roup spacers is incompatible with the receptor interaction required fo r biological activity. Significant diuretic activity is retained with four or fewer methylene groups in this region. C-terminal group analog ues containing -SCH3,-NHCH2CH2OCH3, or -OCH2(C6H5) Offered the greates t retention of diuretic activity while providing increased hydrophobic ity and/or steric bulk. The data are of potential value in the develop ment of mimetic analogues of this insect neuropeptide family. Mimetic analogues are potentially valuable tools to insect neuroendocrinologis ts studying diuresis and/or engaged in the development of future pest management strategies.