title: 2-Methoxy-4-methylsulfinylbenzyl: a backbone amide safety-catch protecting group for the synthesis and purification of difficult peptide sequences.
abstract: The use of 2-methoxy-4-methylsulfinylbenzyl (Mmsb) as a new backbone amide-protecting group that acts as a safety-catch structure is proposed. Mmsb, which is stable during the elongation of the sequence and trifluoroacetic acid-mediated cleavage from the resin, improves the synthetic process as well as the properties of the quasi-unprotected peptide. Mmsb offers the possibility of purifying and characterizing complex peptide sequences, and renders the target peptide after NH4 I/TFA treatment and subsequent ether precipitation to remove the cleaved Mmsb moiety. First, the "difficult peptide" sequence H-(Ala)10-NH2 was selected as a model to optimize the new protecting group strategy. Second, the complex, bioactive Ac-(RADA)4-NH2 sequence was chosen to validate this methodology. The improvements in solid-phase peptide synthesis combined with the enhanced solubility of the quasi-unprotected peptides, as compared with standard sequences, made it possible to obtain purified Ac-(RADA)4-NH2. To extend the scope of the approach, the challenging Aβ(1-42) peptide was synthesized and purified in a similar manner. The proposed Mmsb strategy opens up the possibility of synthesizing other challenging small proteins.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, Barcelona, 08028 (Spain), Fax: (+34) 93-4037126; CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, Barcelona, 08028 (Spain).
authors.forename: Marta
authors.initials: M
authors.lastname: Paradís-Bas
authors.forename: Judit
authors.initials: J
authors.lastname: Tulla-Puche
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry; D001593:Benzyl Compounds / Q000737:chemistry*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013440:Sulfides / Q000737:chemistry*; D014269:Trifluoroacetic Acid / Q000737:chemistry
chemical_list: D000577:Amides; D016229:Amyloid beta-Peptides; D001593:Benzyl Compounds; D010446:Peptide Fragments; D010455:Peptides; C546681:RADA16-I; D013440:Sulfides; C075222:amyloid beta-protein (1-42); C019529:polyalanine; D014269:Trifluoroacetic Acid
keywords: peptides; protecting groups; solid-phase synthesis; synthesis design; synthetic methods