Disfavoring macrocycle b fragments by constraining torsional freedom: the "twisted" case of QWFGLM b6.
While recent studies have shown that for some peptides, such as oligoglycines and Leu-enkephalin, mid-sized b fragment ions exist as a mixture of oxazolone and macrocycle structures, other primary structure motifs, such as QWFGLM, are shown to exclusively give rise to macrocycle structures. The aim of this study was to determine if certain amino acid residues are capable of suppressing macrocycle formation in the corresponding b fragment. The residues proline and 4-aminomethylbenzoic acid (4AMBz) were chosen because of their intrinsic rigidity, in the expectation that limited torsional flexibility may impede "head-to-tail" macrocycle formation. The presence of oxazolone versus macrocycle b(6) fragment structures was validated by infrared multiple photon dissociation (IRMPD) spectroscopy, using the free electron laser FELIX. It is confirmed that proline disfavors macrocycle formation in the cases of QPWFGLM b(7) and in QPFGLM b(6). The 4AMBz substitution experiments show that merely QWFG(4AMBz)M b(6), with 4AMBz in the fifth position, exhibits a weak oxazolone band. This effect is likely ascribed to a stabilization of the oxazolone structure, due to an extended oxazolone ring-phenyl π-electron system, not due to the rigidity of the 4AMBz residue. These results show that some primary structures have an intrinsic propensity to form macrocycle structures, which is difficult to disrupt, even using residues with limited torsional flexibility.
Department of Chemistry, University of Florida, P.O. Box 117200, Gainesville, FL, 32611-7200, USA.
Marcus
M
Tirado
Jochem
J
Rutters
Xian
X
Chen
Alfred
A
Yeung
Jan
J
van Maarseveen
John R
JR
Eyler
Giel
G
Berden
Jos
J
Oomens
Nick C
NC
Polfer
D010129:4-Aminobenzoic Acid / Q000737:chemistry; D020816:Amino Acid Motifs; D041961:Deuterium Exchange Measurement; D007477:Ions / Q000737:chemistry; D007536:Isomerism; D047028:Macrocyclic Compounds / Q000737:chemistry*; D013058:Mass Spectrometry; D009842:Oligopeptides / Q000737:chemistry*; D010081:Oxazolone / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D062366:para-Aminobenzoates
D007477:Ions; D047028:Macrocyclic Compounds; D009842:Oligopeptides; D010446:Peptide Fragments; D062366:para-Aminobenzoates; D010081:Oxazolone; C015668:4-aminomethylbenzoic acid; D011392:Proline; D010129:4-Aminobenzoic Acid