A Strategy To Prepare Peptide Heterodimers in the Solid Phase with an Acid-Labile Linker

Area of Science:

• Chemical Synthesis
• Biochemistry
• Organic Chemistry

Background:

• Current peptide heterodimer synthesis methods are often complex, requiring extensive purification.
• Developing efficient and straightforward synthesis strategies is crucial for peptide-based therapeutics and research.

Purpose of the Study:

• To develop a novel linker for simplified peptide heterodimer preparation.
• To demonstrate the utility of the linker with the Fmoc strategy for on-resin synthesis.
• To provide a convenient method for producing disulfide-linked peptide heterodimers.

Main Methods:

• Preparation of an acid-labile traceless linker compatible with Fmoc solid-phase peptide synthesis.
• On-resin synthesis of peptide heterodimers utilizing the developed linker.
• Concomitant cleavage of the linker and peptide during the final deprotection step.

Main Results:

• Successful synthesis of an acid-labile traceless linker.
• Demonstrated compatibility of the linker with the Fmoc strategy.
• Preparation of two model disulfide-linked peptide heterodimers using the proposed method.
• The synthesis procedure was found to be simple and straightforward.

Conclusions:

• The novel acid-labile traceless linker significantly simplifies the synthesis of peptide heterodimers.
• This method offers a convenient and efficient alternative to existing techniques for preparing disulfide-linked peptide heterodimers.
• The approach is highly compatible with standard solid-phase peptide synthesis protocols.