1. Differentiation of three pairs of Boc-beta,gamma- and gamma,beta-hybrid peptides by electrospray ionization tandem mass spectrometry
V Ramesh, R Srinivas, G V M Sharma, P Jayaprakash, A C Kunwar J Mass Spectrom. 2008 Sep;43(9):1201-14. doi: 10.1002/jms.1393.
A new series of Boc-N-beta(3), gamma(4)-/gamma(4), beta(3)-isomeric hybrid peptides (containing repeats of beta(3)-Caa and gamma(4)-Caa's, Caa = C-linked carbo beta(3)-/gamma(4)-amino acids derived from D-xylose) have been differentiated by both positive and negative ion electrospray ionization (ESI) ion-trap and high resolution quadrupole time-of-flight/tandem mass spectrometry (Q-TOF MS/MS). MS(n) of protonated isomeric peptides and [M+H-Boc+H](+) produce characteristic fragmentation involving the peptide backbone, the Boc-group, and the side chain. The positional isomers are differentiated from one another by the presence of y(n)(+), b(n)(+), and other fragment ions of different m/z values. It is observed that the peptides with beta-Caa at the N-terminus produce extensive fragmentation, whereas gamma-Caa gave rise to much less fragmentation. Peptides with gamma-Caa at the N-terminus lose NH(3), whereas this process is absent for the carbopeptides with beta-Caa at the N-terminus. Two pairs of dipeptide diastereomers are clearly differentiated by the collision-induced dissociation (CID) of their protonated molecules. The loss of 2-methylprop-1-ene is more pronounced for Boc-NH-(R)-beta-Caa-(R)-gamma-Caa-OCH(3) (6) and Boc-NH-(R)-gamma-Caa-(R)-beta-Caa-OCH(3) (12), whereas it is insignificant or totally absent for its protonated diastereomeric pair Boc-NH-(S)-beta-Caa-(S)-gamma-Caa-OCH(3) (1) and Boc-NH-(S)-gamma-Caa-(S)-beta-Caa-OCH(3) (7). Further, ESI negative ion tandem mass spectrometry has also been found to be useful for differentiating these isomeric peptide acids.
2. Electrospray ionization tandem mass spectrometric study on the effect of N-terminal beta- and gamma-carbo amino acids on fragmentation of GABA-hybrid peptides
V Ramesh, M Ramesh, R Srinivas, G V M Sharma, P Jayaprakash Rapid Commun Mass Spectrom. 2008 Nov;22(21):3339-52. doi: 10.1002/rcm.3743.
The fragmentations of protonated and deprotonated ions of a new class of N-blocked hybrid Boc-carbopeptides containing repeats of gamma-Caa/gammaAbu- and beta-Caa/gammaAbu- (Caa==C-linked carbo gamma(4)-/beta(3)- amino acids derived from D-xylose, gammaAbu = gamma-aminobutyric acid) have been studied using electrospray ionization (ESI) ion-trap tandem mass spectrometry (MS/MS). MS/MS of a pair of these protonated diastereomers produces distinct fragmentation of the Boc group. The formation of [M + H-56](+) corresponding to loss of isobutylene is more pronounced for Boc-NH-(R)-gamma-Caa-gammaAbu-OH (2) whereas it is of low abundance for Boc-NH-(S)-gamma-Caa-gammaAbu--OH (1). Similarly, MS(2) of [M--H](-) of 2 produces an abundant [M--H--C(CH(3))(3)OH--CO(2)](-) ion, which is absent for its diastereomeric isomer 1. From this, it can be suggested that MS/MS of N-blocked Boc-protected carbopeptides may be helpful in distinguishing the stereochemistry of the N-terminus Caa. MS(3) of [M + H-Boc + H](+) ions of peptides with a gamma-amino acid (gamma-Caa/gammaAbu) at the N-terminus produces only abundant y(n) (+) ions. On the other hand, characteristic fragmentations involving the peptide backbone (b(n) (+) and y(n) (+)) and the side chain are seen when beta-Caa is at the N-terminus of the peptides. MS(3) of the [M--H--C(CH(3))(3)OH](-) ion of peptides containing gamma-Caa/gammaAbu at the N-terminus gave y(n) (-) and [M--H--C(CH(3))(3)OH--CO(2)](-) ions, whereas the presence of beta-Caa at the N-terminus yielded predominantly [M--H--C(CH(3))(3)OH--HNCO](-). Thus, on the basis of our previous study and that presented here we propose that the fragmentation of these hybrid carbopeptides is highly influenced by the type of carbo amino acid present at the N-terminus.
3. Poly(oxazoline)s with telechelic antimicrobial functions
Christian J Waschinski, Joerg C Tiller Biomacromolecules. 2005 Jan-Feb;6(1):235-43. doi: 10.1021/bm049553i.
Poly(2-alkyl-1,3-oxazoline)s (alkyl = methyl, ethyl) with terminal quarternary ammonium groups were synthesized. It could be shown by NMR and ESI-MS that the termination of the living polymerization with N,N-dimethylalkyl(butyl to hexadecyl)amines was quantitative. The novel functions were investigated regarding their antimicrobial potential toward the bacterium Staphylococcus aureus revealing that only quarternary ammonium functions with 12 and more carbons are antibacterial. Using a novel bifunctional initiator, 3-[(tert-butoxycarbonyl)amino]benzyl-p-toluenesulfonate, poly(oxazoline) with a primary amino group at the starting end and an antimicrobial function at the terminal could be synthesized, as confirmed by NMR and ESI-MS measurements. Comparing the bioactivity of polymers with different functions at the starting end and terminated with dimethyldodecylamine revealed that the starting group has a great effect on the antibacterial properties of the distant terminal. The minimal inhibitory concentrations varied from 0.1 mM for polymer derivatives with a BOC-NH-phenyl starting group to 4 mM for poly(oxazoline)s with a free primary amine at the starting end.
