Determination of the GasPhase Basicities of Proline and its Di- and Tripeptides with Glycine: The Enhanced Basicity of Prolylproline

Ewing, Nigel P.; Zhang, Xin; Cassady, Carolyn J.

doi:10.1002/(sici)1096-9888(199612)31:12<1345::aid-jms430>3.3.co;2-w

Cited by 25 publications

(44 citation statements)

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“…This is the most basic site on a polyproline peptide, and the ProI helix is stabilized with the positive charge located at the N-terminus (unlike alpha helices that are stabilized with the charge located at the C-terminus). Earlier molecular modeling studies of (Pro 2 ϩH) ϩ conducted by Ewing et al [4] also yielded a lowest-energy structure that had both hydrogens on the N-terminal nitrogen involved in hydrogen bonds with the first and second carbonyl oxygens. This consistent pattern of N-terminal charge location over a large range of sizes of polyproline peptides provides an interesting case for studying how the identity and location of the ionizing species affect tandem mass spectrometry (MS/MS) patterns.…”

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confidence: 97%

“…The formation of y-ions from backbone cleavage at the N-terminal side of proline is often the most dominant fragmentation pathway [5,6]. The proton affinity of proline [4] and the strained structure of the complementary b-ion [5] have been proposed as reasons for the selective formation of y-ions. The position of the proline in tri-peptides has been shown to influence the dominance of the so-called proline effect [7][8][9].…”

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MS/MS of protonated polyproline peptides: The influence of N-terminal protonation on dissociation

Unnithan

Myer

Veale

et al. 2007

J. Am. Soc. Mass Spectrom.

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A unique collision-induced dissociation pattern was observed for protonated polyproline peptides of length n in which y nϪ2 and/or y nϪ4 ions were formed in much higher abundance than any other product ions. Cleavage occurs only at every other amide bond, such that product ions are formed only from the losses of even numbers of proline residues. Exclusive losses of even numbers of proline residues were not observed from sodiated peptides. Further study of the tandem mass spectrometry (MS/MS) patterns of protonated proline-rich peptides showed that the substitution of alanine in the second position of polyproline peptides did not prevent the dominant formation of y nϪ2 and y nϪ4 ions. The loss of ProAla to form the y 8 ion from (ProAlaPro 8 NH 2 ϩH) ϩ was as abundant as the loss of ProPro from (Pro 10 NH 2 ϩH) ϩ . However, modification of the peptides that presumably affected the location of the proton on the peptide did alter the MS/MS spectra. Pro 10 and Pro 5 with blocked N-termini or with arginine substituted for the first proline residue did not form abundant y nϪ2 or y nϪ4 ions. MS 3 and double resonance experiments showed that dissociation of intermediate y n product ions can produce y nϪ2 ions, but are not necessary dissociation pathway intermediates. This analysis suggests that the ionizing proton must be located at the N-terminus for the peptide ion to dissociate in this manner. (J Am Soc Mass Spectrom 2007, 18, 2198 -2203) © 2007 American Society for Mass Spectrometry P roline (Pro) is the only naturally occurring amino acid that is bonded to the nitrogen atom of the peptide backbone. The absence of the amide hydrogen prevents polyproline peptides from forming alpha helices. Instead, two possible helical structures of polyproline can be found in solution, named ProI and ProII. ProI exists in solution as a right-handed helix with 3.3 residues per turn, and all peptide bonds are cis bonds. ProII is a left-handed helix with 3.0 residues per turn, and all peptide bonds are trans bonds. The type of helix formed varies with the type of solvent in which the polyproline is dissolved. ProI is found in less protic solvents such as butanol or propanol, whereas ProII exists in more protic solvents such as water. Counterman and Clemmer [1] have shown with ion mobility spectrometry and supporting computational studies that when polyproline peptides are introduced into the gas phase from propanol solutions, features of the ProI helix persist in the gas phase. This was observed for many different lengths of polyproline chains. However, electrospray ionization (ESI) of aqueous solutions did not produce ion mobility data consistent with ProII helices. It was reasoned that the elongated structure of the ProII helix could not be stabilized in the absence of solvent [1,2]. It already has been established that the solvent choice has no effect on the dissociation energetics of polyproline peptides [3]. Interestingly, a unifying feature was established for all polyproline peptides examined, regardless of the original solvent....

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MS/MS of protonated polyproline peptides: The influence of N-terminal protonation on dissociation

Unnithan

Myer

Veale

et al. 2007

J. Am. Soc. Mass Spectrom.

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“…Earlier studies on the gas-phase basicities of small peptides suggest that the sequences of the peptides influence the measured basicities [43,45]. For example, ProGlyGly is more basic than GlyGlyPro [43].…”

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“…In recent years, many of the gas-phase studies have focused on the determination of the proton affinities (and gas-phase basicities) of amino acids and peptides [33][34][35][36][37][38][39][40][41][42][43][44][45]. Although the gas-phase acidities of isolated amino acids have been studied extensively [46 -54], and the apparent acidities of multiply charged peptides have been reported [55], the information on the acidities of gas-phase neutral peptides is very limited [56,57].…”

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Gas-phase acidities of cysteine-polyglycine peptides: The effect of the cysteine position

Morishetti

Huang

Yates

et al. 2010

J. Am. Soc. Mass Spectrom.

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The sequence and conformational effects on the gas-phase acidities of peptides have been studied by using two pairs of isomeric cysteine-polyglycine peptides, CysGly 3,4 NH 2 and Gly 3,4 CysNH 2 . The extended Cooks kinetic method was employed to determine the gas-phase acidities using a triple quadrupole mass spectrometer with an electrospray ionization source. The ion activation was achieved via collision-induced dissociation experiments. The deprotonation enthalpies (⌬ acid H) were determined to be 323.9 Ϯ 2.5 kcal/mol (CysGly 3 NH 2 ), 319.2 Ϯ 2.3 kcal/mol (CysGly 4 NH 2 ), 333.8 Ϯ 2.1 kcal/mol (Gly 3 CysNH 2 ), and 321.9 Ϯ 2.8 kcal/mol (Gly 4 CysNH 2 ), respectively. The corresponding deprotonation entropies (⌬ acid S) of the peptides were estimated. The gas-phase acidities (⌬ acid G) were derived to be 318.4 Ϯ 2.5 kcal/mol (CysGly 3 NH 2 ), 314.9 Ϯ 2.3 kcal/mol (CysGly 4 NH 2 ), 327.5 Ϯ 2.1 kcal/mol (Gly 3 CysNH 2 ), and 317.4 Ϯ 2.8 kcal/mol (Gly 4 CysNH 2 ), respectively. Conformations and energetic information of the neutral and anionic peptides were calculated through simulated annealing (Tripos), geometry optimization (AM1), and single point energy calculations (B3LYP/6-31ϩG(d)), respectively. Both neutral and deprotonated peptides adopt many possible conformations of similar energies. All neutral peptides are mainly random coils. The two C-cysteine anionic peptides, Gly 3,4 (Cys-H) Ϫ NH 2 , are also random coils. The two N-cysteine anionic peptides, (Cys-H) Ϫ Gly 3,4 NH 2 , may exist in both random coils and stretched helices. The two N-cysteine peptides, CysGly 3 NH 2 and CysGly 4 NH 2 , are significantly more acidic than the corresponding C-terminal cysteine ones, Gly 3 CysNH 2 and Gly 4 CysNH 2 . The stronger acidities of the former may come from the greater stability of the thiolate anion resulting from the interaction with the helix-macrodipole, in addition to the hydrogen bonding interactions. (J Am Soc Mass Spectrom 2010, 21, 603-614)

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Amide Cis ‐ Trans Isomerization in Peptides and Proteins

Wawra

Fischer

2006

Cis‐trans Isomerization in Biochemistry

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Imidic and secondary amide peptide bonds, echoing motifs of the backbone of oligopeptides and proteins, are among the most widespread functional groups of bioactive molecules. Nineteen out of the 20 gene-coded amino acids form secondary amide peptide bonds, whereas the peptide bond preceding proline is imidic in its chemical nature. Planarity and strong conformational preferences are general features of peptide bonds. Nevertheless, slight deviation from planarity is common in folded polypeptide chains [1][2][3]. The cis-trans isomers of simple secondary and substituted tertiary amides, such as N-methyl acetamide and N,N-dimethyl acetamide respectively, because of the predictive capability of their molecular parameters, have often been used for the analysis of thermodynamics and kinetics of cis-trans isomerization (CTI) in polypeptide chains. This field is covered by many reviews [4][5][6][7][8]. Thus, restrictions in the number of energy minima in peptide bond torsion (dihedral angle x) as well as in the ease in surmounting the energy barrier separating the isomers is in keeping with the classic view of amide bond resonance, and is best illustrated by assuming a partial double bond character of the C-N bond of the peptide unit ( Fig. 9.1) [9]. For simple amides, geometric isomers with the angle x » 0 (cis) and x » 180 (trans) coexist in solution as demonstrated in the mid 1950s, together with the slow C-N bond rotation by 1 H NMR spectroscopy for dimethyl formamide. The barriers of rotation can be calculated from the rate constants of CTI yielding DG ‡ values for N-methyl acetamide of 79 kJ mol -1 for the cis to trans transition and DG ‡ = 89 kJ mol -1 for the reverse reaction (30 C, water) [10]. Detailed knowledge on the thermodynamic origin of CTI remains nonetheless limited, and predictions of ratios of isomers and barrier heights across different chemical structures are difficult. In the transition state of peptide bond rotation, twisted C (carbonyl) as well as N pyramidal configurations cis-trans Isomerization in Biochemistry. Edited by Christophe Dugave have to be considered. Indeed, ground-state nonplanarity causes reduction of the rotational barriers in a series of constrained amides [11].Clearly, CTI leads to a periodic backbone contraction/expansion of the polypeptide chain involved, as could be inferred from the isomer-specific distances of the C a atoms directly attached to the isomerizing peptide bond. For prolyl bonds in native proteins this distance is about 0.8 shorter in the cis isomer when compared to the respective trans isomer [12]. This atomic translation produces a mechanical moment that was hypothesized to be involved in the functional cycle of motor proteins [13].Provided that stabilizing tertiary interactions or steric constraints are absent in the respective molecules, secondary amides show a preference for the trans isomer in solution. It is obvious that the cis form is energetically less stable due to steric repulsion of the neighboring C a atoms. The steric advantage of the trans conf...

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Determination of the GasPhase Basicities of Proline and its Di- and Tripeptides with Glycine: The Enhanced Basicity of Prolylproline

Cited by 25 publications

References 4 publications

MS/MS of protonated polyproline peptides: The influence of N-terminal protonation on dissociation

MS/MS of protonated polyproline peptides: The influence of N-terminal protonation on dissociation

Gas-phase acidities of cysteine-polyglycine peptides: The effect of the cysteine position

Amide Cis ‐ Trans Isomerization in Peptides and Proteins

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