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W F Haddon

Publications and source records attributed to W F Haddon.

22 records · Page 2Linked to original sources
PubMedDate not supplied

Structure-activity relationships for myotropic activity of the gastrin/cholecystokinin-like insect sulfakinins.

The sulfakinins constitute a family of real and putative peptide sequences characterized from the cockroach Leucophaea maderae (leucosulfakinin subfamily) and fruitfly Drosophila melanogaster (drosulfakinin subfamily) with homology to the sulfated mammalian hormones gastrin II and cholecystokinin (CCK). The leucosulfakinin (LSK) subfamily of neuropeptides stimulate contractions of the isolated cockroach hindgut. In this paper, we have ascertained some of the primary structural requirements of the sulfakinins for myotropic (muscle-contracting) activity. The myotropic "active core" of this family has been determined to be the C-terminal hexapeptide, though the C-terminal octapeptide (Glu-Asp-Tyr(SO3H)-Gly-His-Met-Arg-Phe-NH2) is required for full activity. The LSKs demonstrate considerable tolerance to Ala substitution in positions 7 and 9 within the active core without complete loss of activity. Conversely, Ala substitution in positions 8, 10 and 11 led to inactive compounds. Basicity is a critical feature of LSK position 10, while aromatic character is an important characteristic for positions 8 and 11 for myotropic activity. Only trace activity could be observed upon replacement of the Tyr(SO3H) residue in LSK-position 6 with a Ser(SO3H). One analog ([3MeHis8] LSK) proved more active as a contractile stimulant than the natural product, while another ([7-11,Tyr(SO3H)7] LSK), conversely, demonstrated inhibition of spontaneous contractions of the cockroach hindgut.

Amino Acid Sequence↗
PubMedDate not supplied

Two dihydropyrrolizine alkaloid metabolites isolated from mouse hepatic microsomes in vitro.

The in vitro mouse hepatic microsomal metabolism of the macrocyclic pyrrolizidine alkaloid senecionine was studied for additional metabolites. Using previously developed HPLC systems plus a preparative system, two additional dihydropyrrolizine metabolites have been identified from the microsomal enzyme system of mice. The metabolites 1-hydroxymethyl-7-methoxy-6,7-dihydro-5H-pyrrolizine (methoxydehydroretronecine) and 1-formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (hydroxydanaidal) have not been heretofore isolated from mouse microsomal enzyme systems. The metabolite dehydroretronecine which had previously been isolated from rat hepatic microsomes, was not detected while senecic acid, 19-hydroxysenecionine, and senecionine N-oxide were again present.

Animals↗