R2R01: A long-acting single-chain peptide agonist of RXFP1 for renal and cardiovascular diseases.

Background: The therapeutic potential of relaxin for heart failure and renal disease in clinical trials is hampered by the short half-life of serelaxin. Optimization of fatty acid-acetylated single-chain peptide analogues of relaxin culminated in the design and synthesis of R2R01, a potent and selective RXFP1 agonist with subcutaneous bioavailability and extended half-life.

Experimental Approach: Cellular assays and pharmacological models of RXFP1 activation were used to validate the potency and selectivity of R2R01.

Fatty acid acylated peptide therapeutics: discovery of omega-n oxidation of the lipid chain as a novel metabolic pathway in preclinical species.

We recently described C18 fatty acid acylated peptides as a new class of potent long-lasting single-chain RXFP1 agonists that displayed relaxin-like activities in vivo. Early pharmacokinetics and toxicological studies of these stearic acid acylated peptides revealed a relevant oxidative metabolism occurring in dog and minipig, and also seen at a lower extent in monkey and rat. Mass spectrometry combined to NMR spectroscopy studies revealed that the oxidation occurred, unexpectedly, on the stearic acid chain at ω-1, ω-2 and ω-3 positions.

Causes of Botulinum Toxin Treatment Failure.

Purpose: The purpose of this article is to review the cause of botulinum toxin (BT) failure and determine the ways to minimize the risks of its occurrence.

Methods: A PubMed and Google Scholar literature search was conducted with the search terms botulinum toxin, treatment, failure, causes, and prevention. Fifteen relevant articles were found and used as the scientific base for this article.

Impact of Cyclization and Methylation on Peptide Penetration through Droplet Interface Bilayers.

Cell-penetrating peptides enter cells via diverse mechanisms, such as endocytosis, active transport, or direct translocation. For the design of orally delivered cell-penetrating peptides, it is crucial to know the contribution of these different mechanisms. In particular, the ability of a peptide to translocate through a lipid bilayer remains a key parameter for the delivery of cargos.