Key result
Modified ANP analogues boost in vitro stability but fail to prolong in vivo half-life.
Why the study?
The degradation pathway of a prototypical small ANP analogue and strategies to improve its stability were not fully characterized.
Modifications to the N- and C-termini of ANP analogues improved in vitro stability but failed to extend in vivo half-lives.
May guide ANP analogue design; leaves open in vivo efficacy and clinical utility.
The degradation of a prototypical small analogue of atrial natriuretic peptide (ANP) has been studied using HPLC and mass spectrometric techniques. These studies revealed that removal of the N-terminal amino acid was the primary catabolic event in vitro. Based on this information the N-terminus was remanufactured to provide a family of more stable analogues. Additional stabilization was provided through modification of the C-terminal tripeptide. Through dramatically more stable in vitro, these new analogues do not appear to have longer in vivo half-lives.
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Devine et al. (1992) studied this question. Remanufactured small analogues of atrial natriuretic peptide (ANP) was evaluated on In vitro stability and in vivo half-lives. Remanufactured ANP analogues with modified N- and C-termini were dramatically more stable in vitro but did not appear to have longer in vivo half-lives.
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