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Successful synthesis of a glial‐specific blood–brain barrier shuttle peptide following a fragment condensation approach on a solid‐phase resin
Author(s) -
Al Musaimi Othman,
Morse Sophie V.,
Lombardi Lucia,
Serban Simona,
Basso Alessandra,
Williams Daryl R.
Publication year - 2023
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3448
Subject(s) - fragment (logic) , peptide , amino acid , peptide synthesis , chemistry , combinatorial chemistry , condensation , phase (matter) , solid phase synthesis , reagent , stereochemistry , biochemistry , organic chemistry , computer science , physics , programming language , thermodynamics
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.