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ZENODO
Preprint . 2026
License: CC BY
Data sources: ZENODO
ZENODO
Preprint . 2026
License: CC BY
Data sources: Datacite
ZENODO
Preprint . 2026
License: CC BY
Data sources: Datacite
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Design Rationale for a Retroinverso 4-Fluorophenylalanine SS-31 Analogue (RI-4FPhe-SS31)

Authors: Seto, Karsten;

Design Rationale for a Retroinverso 4-Fluorophenylalanine SS-31 Analogue (RI-4FPhe-SS31)

Abstract

This document describes the design rationale, predicted properties, and molecular specification for RI-4FPhe-SS31, a retroinverso analogue of the mitochondria-targeted tetrapeptide SS-31 (elamipretide, D-Arg-Dmt-Lys-Phe-NH2) incorporating a 4-fluorophenylalanine substitution. The two modifications address independent metabolic vulnerabilities of the parent compound: the retroinverso backbone confers resistance to endogenous peptidases, while the 4-fluorine substitution on the C-terminal phenylalanine blocks CYP450-mediated aromatic hydroxylation. The combined effect is predicted to extend the plasma half-life of the molecule while preserving the net +3 charge and the spatial arrangement of cationic and aromatic side chains required for selective interaction with cardiolipin at the inner mitochondrial membrane. This document is published as prior art under CC-BY 4.0 to ensure permanent public domain availability.

Keywords

SS-31, Elamipretide, Cardiolipins/chemistry, Mitochondria/chemistry, Peptidomimetics, Peptidomimetics/chemistry, Retroinverso, 4-fluorophenylalanine, Prior Art, Mitochondria

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average