Acid‐Stable Ester Linkers for the Solid‐Phase Synthesis of Immobilized Peptides

0525588 - ÚOCHB 2021 RIV DE eng J - Journal Article
Pícha, Jan - Buděšínský, Miloš - Mitrová, Katarína - Jiráček, Jiří
Acid‐Stable Ester Linkers for the Solid‐Phase Synthesis of Immobilized Peptides.
ChemPlusChem. Roč. 85, č. 6 (2020), s. 1297-1306. ISSN 2192-6506. E-ISSN 2192-6506
R&D Projects: GA MŠMT(CZ) EF16_019/0000729
Institutional support: RVO:61388963
Keywords : diketopiperazines * esters * peptides * protecting groups * solid-phase synthesis
OECD category: Organic chemistry
Impact factor: 2.863, year: 2020
Method of publishing: Limited access
https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cplu.202000246

A series of N‐terminally Fmoc‐protected linkers of the general formula Fmoc‐X−CO−O−Y−COOH have been prepared, where X is −NH−CH2−CH2‐ or ‐p‐(aminomethyl)phenyl‐ and Y is −(CH2)n− (n is 1 or 4) or ‐p‐(methyl)phenyl‐. These linkers can easily be covalently attached via their C‐terminal carboxyl group to a resin bearing a free amino group. After cleavage of the N‐terminal Fmoc group, the linkers can be extended by standard solid‐phase peptide synthesis techniques. These ester linkers are acid‐stable and resistant to the base‐mediated diketopiperazine formation that often occurs during the synthesis of ester‐bound peptides, they are stable at neutral pH in aqueous buffers for days but can be effectively cleaved with 0.1 m NaOH or aq. ammonia within minutes or hours, respectively. These properties make these ester handles well suited for use as linkers for the solid‐phase peptide synthesis of immobilized peptides when the stable on‐resin immobilization of the peptides and the testing of their biological properties in aqueous buffers at neutral pH are necessary.
Permanent Link: http://hdl.handle.net/11104/0309699