N-Methylated peptides

Fig. 10. Structures of nonribosomally synthesized peptides of bacterial origin (1-6) and fungal origin (7-9). Me, N-methylated peptide boni Orn, ornithine 4-MHA, 4-methyl-3-hydroxyanthranilic acid Aad, aminoadipic acid Aeo, 2-amino-9,10-epoxy-8-oxodecanoic acid D-Hiv, D-hydroxyisovaleric acid Bmt, (4i )-4-[( )-2-butenyl]-4-methyl-L-threonine Abu, a-aminoisobutyric acid Sar, sarcosine. The boxes signify gene products for peptide synthetases composed of modules which activate and process the indicated amino acids...

The transporter does also accept some dipeptides with a N-methylated peptide bond exemplified by Gly-Sar and some tripeptides with N-methylated amide bond however, N-methylation does not seem to be a general stabilization approach, since the affinity for PEPT1 is not retained for all the investigated compounds [113, 114],... 

Gao, J., Sudoh, M., Aube, J. and Borchardt, R.T. (2001) Transport characteristics of peptides and peptidomimetics I. N-methylated peptides as substrates for the oligopeptide transporter and P-glycoprotein in the intestinal mucosa. The Journal of Peptide Research, 57 (4), 316-329. 

DBU, DMF, HSCH2CH2OH, >48% yield. These conditions were used to remove the nosyl group from N-methylated peptides. ... 

Finally, the dlllll stereoisomer of enniatin B retains the characteristic disk shape of beauvericin and the ldldld enniatin, with the isopropyl groups directed to the periphery of the disk and a sizable cavity within the ring. The principal difference in the dlllll stereoisomer is the occurrence of one cis N-methyl peptide group (Shishova and Simonov, 1977). This group of molecules does not possess any NH groups available for hydrogen bond formation. 

Likewise, in the synthesis of unmethylated analogs of N-methyl-peptides, rates decrease dramatically to about 10% for each unmethylated residue. Thus, de-dimethyl or de-trimethyl compounds are rarely observed. 

Billich A. Zocher R. Biosynthesis of N-methylated peptides. Kleinkauf H, von Dohren H, eds. Biochemistry of Peptide Antibiotics. Berlin de Gruyter 1990, 57-80. 

Synthesis of N-Methylated Peptides On-Resin iiliethyiation and iiliicrowave-Assisted Coupiings... 

Key words Solid-phase peptide synthesis, N-methylation, N-methylated peptides. Pharmacokinetics, Bioactive peptide, o-Nitrobenzenesulfonyl protecting group. Difficult couplings. Microwave heating,... 

Structural preferences, and therefore, it is an attractive design strategy (Roodbeen et al., 2012), However, the synthesis of N-methylated peptides can be challenging as the nucleophile in the acylation step is a sterically hindered secondary amine. They have systematically evaluated the use of microwave heating, different coupling conditions and the role of steric effects on coupling yields. 

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