Differentiation of Boc‐N‐protected α/β‐hybrid peptides containing β‐Caa‐L‐Ala‐β‐Caa‐OMe and β‐Caa‐L‐Ala‐β‐Caa‐NHMe at the C‐terminus by electrospray ionization tandem mass spectrometry

Abstract

Differentiation of Boc-N-protected a/b-hybrid peptides containing b-Caa-L-Ala-b-Caa-OMe and b-Caa-L-Ala-bCaa-NHMe at the C-terminus by electrospray ionization tandem mass spectrometryOver the past few years, there has been growing interest in peptides derived from non-natural amino acids because of their importance in pharmaceutical and foldamer chemistry. [1][2][3] Such efforts have invariably been to understand their conformational behavior and develop them into biomolecules with novel properties. The b-peptides, a very important class in the foldamer domain, derived from b-amino acids, exhibited several novel secondary structures.[4] The fundamental structural element in proteins is the b-strand, which is known to be conformationally suitable for specific recognition by bimolecular receptors such as proteolytic enzymes, major histocompatibility complex (MHC) proteins and transferases. [5][6][7] A 12/10-mixed helix unique to the b-peptides was discovered -Caa) with alternating chirality at the Cb carbon.[5] It was also shown in their studies on peptides with alternating b-Caa and b-h-Gly, the formation of right-as well as lefthanded 10/12-and 12/10-helices.[6] They also demonstrated that the a/b-hybrid peptides containing alternating L-Ala and b-Caa, with the L-Ala-b-Caa-L-Ala (a-b-a) sequence at the C-terminus, formed very robust 11/9 mixed helices [9] and the a/b-hybrid peptides with the b-Caa-L-Ala-b-Caa (b-a-b) sequence at the C-terminus formed an unusual and novel three residue (b-a-b) turn at the C-terminus, nucleated by an 11/9 helix at the N-terminus, thus resulting in a rather well-defined helix-turn (HT) motif in these peptides. [10] Mass spectral characterization of a-amino acid peptides is well documented in the literature. [11][12][13] The tandem mass spectrometry (MS/MS) of protonated peptides [14][15][16] formed in electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) [17] has been an established tool in determining amino acid sequence of peptides. There are

Characterization of N‐Boc/Fmoc/Z‐N′‐formyl‐gem‐diaminoalkyl derivatives using electrospray ionization multi‐stage mass spectrometry

“…Tandem mass spectrometry (MS/MS) in electrospray ionization (ESI) is an established technique for the structure elucidation of peptides [35][36][37][38][39][40][41][42][43][44][45][46] and peptidomimetics, [47][48][49][50][51][52][53][54][55][56][57] but the characterization of peptides containing a gem-diaminoalkyl moiety has received little attention. [58][59][60][61] This has prompted us to undertake a detailed mass spectrometric study on a series of N-alkoxycarbonyl-N′-formyl-gemdiaminoalkyl derivatives using the ESI technique both in the positive and negative ion mode.…”