Building blocks for the synthesis of post‐translationally modified glycated peptides and proteins

Abstract

Growing interest in synthetic peptides carrying post-traslational modifications, in general, and the Amadori modification in particular, raises the need for specific building blocks that can be used in stepwise peptide synthesis. Herein, we report the synthesis of N(alpha)-Fmoc-Lys-OH derivatives containing N(epsilon)-1-deoxyfructopyranosyl moiety.

Hydrate of 2,3:4,5-di-O-isopropylidene-β-D-arabino-hexos-2-ulo-2,6-pyranose as new crystalline reagent in the preparation of Amadori derived peptides

“…Compound II was also tested in synthesis of (Nα-9-fluorenylmethoxycarbonyl-N ε-te r t-b u ty l o x y c a r b o n y l -N ε-N -( 2 ,3 :4 ,5 -d i -Oisopropyliden-1-deoxy-β-D-fructopyranose-1-ylo)lysine, Fmoc-Lys(i,i-Fru,BOC)-OH (III), which is a building block useful for incorporating the glycated lysine moiety into the peptide chain. 7,8 The product III was obtained by reductive alkylation of Fmoc-Lys-OH trifluoroacetate in THF using compound II in the presence of sodium cyanoborohydride. After the glycation, the secondary amino group of lysine was protected using Boc 2 O.…”

“…The 2, 3:4, 5 -di-O-isopropylidene-β-D-arabinohexos-2-ulo-2,6-pyranose (I) is a common reagent used for solid [5][6][7][8] and solution [9,10] phase synthesis of peptide derived Amadori products by reductive alkylation of the ε-amino groups of the lysine residue or N-terminal α-amino groups in the presence of sodium cyanoborohydride. Previously the same reagent was also applied for synthesis of natural products, talatomycins A, B and 1-deoxy-6-castanospermine [11,12].…”

Multi-Stage Mass Spectrometry Analysis of Sugar-Conjugated β-Turn Structures to be Used as Probes in Autoimmune Diseases

“…Subsequent dehydration, condensation, fragmentation, oxidation, and cyclization reactions lead to the irreversible formation of advanced glycation end products (AGEs). Glycation of CSF114 was achieved introducing at position 7 the completely protected building block Fmoc-L -Lys(Boc)(2,3:4,5-di-O -isopropylidene-1-deoxyfructopyranosyl)-OH, previously described [26]. Glycation induces a mass shift of 162 Da on the modified residue.…”

Orthogonal Protecting Groups and Side‐Reactions in Fmoc/tBu Solid‐Phase Peptide Synthesis

“…Usually the goal is to introduce, on a given sequence, post-translational modifications such as glycations [102] and glycosylations [103] or taking advantage of the ability to form amide bonds between Lys side-chains and molecular devices bearing carboxylic groups [104]. This latter application applies to a broad range of peptide modifications, like linking to chromophores, chelating agents, radioactive molecules, and many more substituents each conferring a specific property to the modified peptide.…”

“…The coupling rate is slower for bulky amino acids such as Val and Leu, which have a branching at the b-carbon atom. Similar considerations, of slow coupling induced by steric hindrance, apply to unusual amino acids, those carrying special modifications (e.g., post-translational modifications), or chromophore groups [102][103][104].…”