Design Description

Artifact name

SCIDEX-SS31-ALT-01

One-line description

A research-only SS-31-like tetrapeptide surrogate, H-Arg-Tyr-Lys-Trp-NH2 (RYKW), proposed as a hypothesis-generating cardiolipin-facing membrane binder for mitochondrial inner-membrane studies.

Rationale

This candidate preserves the core SS-31 design logic described in the source literature:

• short tetrapeptide length

• alternating cationic and aromatic side chains

• compact sequence suitable for membrane interaction studies

• emphasis on cardiolipin-rich inner mitochondrial membrane behavior

The specific change from the SS-31 reference motif is the use of tryptophan in place of phenylalanine to increase aromatic bulk and provide a different aromatic interaction surface. This is only a design hypothesis. It does not imply improved function, safety, or translational value.

Sequence representation

• Canonical surrogate sequence: RYKW

• Modified peptide notation: H-Arg-Tyr-Lys-Trp-NH2

What this is not

• Not a medical recommendation

• Not a therapeutic claim

• Not a validated mitochondrial drug candidate

• Not an optimized structure

Expected qualitative properties

• Two cationic residues should support electrostatic interaction with anionic lipid environments.

• Two aromatic residues should support membrane association and a compact SS-31-like pattern.

• The alternating register should keep the sequence in the same design family as the reference compounds.

Uncertainty statement

The mechanistic link between sequence choice and cardiolipin stabilization remains uncertain. The reference literature supports the broader motif class, but not this exact surrogate sequence.

Suggested next experiments

• Compare RYKW against SS-31 and a scrambled control in cardiolipin-containing membrane assays.

• Measure binding or partitioning under matched salt and lipid-composition conditions.

• Assess whether the candidate changes membrane electrostatics in a direction consistent with the SS-31 literature.

• Check whether the peptide adopts a compact membrane-associated conformation or remains more extended than SS-31.