Successful synthesis of a glial‐specific blood–brain barrier shuttle peptide following a fragment condensation approach on a solid‐phase resin. (28th August 2022)

• Record Type: Journal Article
• Authors: Al Musaimi, Othman; Morse, Sophie V.; Lombardi, Lucia; Serban, Simona; Basso, Alessandra; Williams, Daryl R.
• Is Part Of: Journal of peptide science. Volume 29:Number 2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-28
• Subjects: blood–brain barrier shuttle -- cell‐penetrating peptides -- fragment condensation -- solid‐phase peptide synthesis; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3448
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Successful manual synthesis of the TD2.2 peptide acting as a blood–brain barrier shuttle was achieved. TD2.2 was successfully synthesised by sequential condensation of four protected peptide fragments on solid‐phase settings, after several unsuccessful attempts using the stepwise approach. These fragments were chosen to minimise the number of demanding amino acids (in terms of coupling, Fmoc removal) in each fragment that are expected to hamper the overall synthetic process. Thus, the hydrophobic amino acids as well as Arg(Pbf) were strategically spread over multiple fragments rather than having them congested in one fragment. This study shows how a peptide that shows big challenges in the synthesis using the common stepwise elongation methodology can be synthesised with an acceptable purity. It also emphasises that choosing the right fragment with certain amino acid constituents is key for a successful synthesis. It is worth highlighting that lower amounts of reagents were required to synthesise the final peptide with an identical purity to that obtained by the automatic synthesiser. Abstract : Successful manual synthesis of the TD2.2 peptide, which acts as a blood–brain barrier shuttle, was achieved by sequential condensation of four protected peptide fragments on a solid‐phase resin. The chosen fragments minimised the number of demanding amino acids in each fragment, facilitating the overall synthetic process.