Add time:09/02/2019         Source:sciencedirect.com

Four modified atrial natiuretic factor (ANF) analogs were designed and synthesized by the solid-phase method. Using human ANF-(99–126) as the reference compound the receptor binding affinity and biological activity of these analogs were examined by radioreceptor assay and in vivo experiments. PLO68, a 21 amino peptide with structural modifications des-Ser103,104-[Mpr105, D-Ala107,114]APII-amide exhibited 2.5 and 2.2 fold more activity than human ANF-(99–126) in lowering blood pressure and causing natriuresis in urethane anesthetized rats. Receptor binding assays using rat lung membranes showed that PLO68 had a Kd of 200 ± 12 pM compared to a Kd of 620 ± 12 pM for human ANF-(99–126). Similar chemical modifications, except for substitution of glycine and alanine at the positions 115 and 118, and 120 by D-alanine resulted in three analogs PLO63 and PLO64, PLO67 respectively. PLO63, PLO64 and PLO69 had similar affinities and in vivo potency as human ANF-(99–126). These data suggest that the structural modifications made in PLO68 can cause an increase in the receptor binding ability and an enhancement of biological activities.

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