The 10th Asia-Oceania Mass Spectrometry Conference (AOMSC2025) - organized by the Mass Spectrometry Society of Japan

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Plenary Lecture

Day 3, June 24(Tue.) 8:15-9:15

Room A (Maesato West), Room B (Maesato Center), Room C (Top of Yaima)

  • 3-PL-0815
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From Toxins to Therapeutics: Atrial Natriuretic Peptide Analogs for the Tailored Treatment of Acute Decompensated Heart Failure

(1Natl Univ Singapore, 2VCU Richmond VA)
oManjunatha Kini1,2

Congestive heart failure (CHF) is a long-term condition when the heart cannot pump blood well enough to provide a normal supply to the body. CHF can get worse quickly leading to Acute Decompensated Heart Failure (ADHF). In this life-threatening condition, patients show abrupt deterioration of hemodynamic stability, pulmonary edema and decline in renal function. Based on the evidence for congestion and low cardiac output, ADHF patients are classified as “Warm and wet", “Cold and wet", “Warm and dry", and “Cold and dry" presentations. Each sub-type of presentation needs specific treatment. The unmet need is for a menu of agents allowing controlled vasodilation without excess diuresis and effective diuresis without excess lowering of blood pressure. Here, I describe the design of two human ANP analogues for the treatment of ADHF patients: DGD-ANP increases urine volume without affecting blood pressure, while DRD-ANP reduces blood pressure with no effect on urine production in anesthetized rats and in conscious normal and heart failure sheep models. Thus, one residue difference results in (a) two opposite ends of spectrum of pharmacology; (b) altered kinetics of cGMP production by NPR-A; (c) structural changes in the ligands; and (d) induces distinct conformational changes in the receptor NPR-A.