Icotrokinra KSM Amino Acid Derivatives Fmoc-Sar-OH CAS NO. 77128-70-2

Fmoc-Sar-OH is N-Fmoc-N-methylglycine. Compared with regular glycine (NH-CH₂-COOH), Sarcosine contains an additional methyl group on the nitrogen atom (N(CH₃)-CH₂-COOH). After incorporation into a peptide chain, it forms an N-methylated peptide bond, which can significantly influence peptide stability and conformation.

Icotrokinra (JNJ-77242113) is an oral IL-23 receptor antagonist peptide. N-methyl amino acids such as Sarcosine are commonly introduced into oral peptides to improve their drug-like properties, especially stability against enzymatic degradation and oral bioavailability.

Improved resistance to enzymatic degradation: Normal peptide bonds (–CO–NH–) are easily recognized and cleaved by proteases. After N-methylation (–CO–N(CH₃)–), the removal of the N–H hydrogen reduces hydrogen bonding interactions with enzymes, decreases protease recognition, and improves peptide stability.

Optimization of peptide conformation: N-methylation can influence backbone flexibility, peptide folding, and receptor-binding conformation, helping maintain the active structure required for target interaction.

Improvement of oral bioavailability: Compared with conventional peptides that are easily degraded in the gastrointestinal tract, N-methylated peptides usually show improved metabolic stability and higher potential for oral absorption.

Fmoc-Sar-OH is introduced as a specialized building block during Fmoc solid-phase peptide synthesis (Fmoc-SPPS). The typical process includes resin loading, Fmoc deprotection, coupling of Fmoc-Sar-OH, repeated chain elongation, cleavage, and purification to obtain the final modified peptide API.