Soluble non-cross-linked poly(norbornene) supports for peptide synthesis with minimal reagents.
Solid-phase peptide synthesis has been an attractive method for synthesizing peptides because it is quick and can be automated. The heterogeneous reaction medium in solid-phase peptide synthesis necessitates the use of large equivalents of reagents to drive the reactions to completion. Peptide synthesis using soluble, yet isolable, supports is an attractive alternative to solid-phase peptide synthesis. Reported herein is a soluble poly(norbornene)-derived support containing multiple attachment sites for high loading capacities and solubilizing oligoether/alkyl groups. The Ala-attached support has been used to synthesize tri- to octapeptides in 28 to 97% yields using only 1.2 equiv of amino acids and coupling reagents. The acyclic hexapeptide precursor to natural product segatalin A was synthesized in 41% yield on the support using one-eighth of the equivalents of coupling reagents compared to that in reported procedures. The support could be recovered in up to 98% yield after peptide synthesis, and the recovered support was utilized to synthesize tri- and tetrapeptides that contain amino acids other than Ala at the C-terminus in ca. 80% yields.
Department of Chemistry, Indian Institute of Technology Madras , Chennai, 600036 Tamil Nadu, India.
Nimmashetti
N
Naganna
Nandita
N
Madhavan
D000409:Alanine / Q000737:chemistry*; D055598:Chemical Phenomena; D007202:Indicators and Reagents / Q000737:chemistry*; D015394:Molecular Structure; D009636:Norbornanes / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D012995:Solubility
D007202:Indicators and Reagents; D009636:Norbornanes; D009842:Oligopeptides; D010455:Peptides; C000599075:segatalin A; D000409:Alanine