Side-chain effects on the structures of protonated amino acid dimers: A gas-phase infrared spectroscopy study

AbstractThe primary intermediates resulting from the interaction of cisplatin, cis-(PtCl2(NH3)2], most widespread antitumor drug, with biomolecular targets are characterized. Electrospray ionization is used to deliver ions formed in solution into the gas phase where they are structurally interrogated by vibrational “action” spectroscopy in conjunction with quantum chemical calculations. The aquation products, cis-[PtX(NH3)2(H2O)]+ (X = Cl, OH), lying along the path responsible for biological activity, are shown to display distinctive features responding to ligation pattern and optimized geometry. The IR spectra of trans-[PtX(NH3)2(H2O)]+ are different, testifying that cis and trans complexes are stable, non interconverting species both in solution and in the gas phase. Ligand substitution by simple nucleophiles (L = pyridine, 4(5)-methylimidazole, thioanisole, trimethylphosphate, acetamide, dimethylacetamide, urea and thiourea) yields cis-[PtCl(NH3)2(L)]+ complexes displaying remarkable regioselectivity whenever L presents multiple candidate platination sites. The incipient formation of cisplatin-derived complexes with the recognized biological amino acid targets L-histidine (His) and L-methionine (Met) has been investigated revealing the primary platination event to be mainly directed at the Nπ atom of the imidazole side chain of His and to the thiomethyl sulfur of Met. The isomer and conformer population of the ensuing cis-[PtCl(NH3)2(Met/His)]+ complexes, sampled in the gas phase, can be ascertained by photofragmentation kinetics on isomer/conformer specific resonances.

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Experimental and theoretical investigations of infrared multiple photon dissociation spectra of lysine complexes with Zn2+ and Cd2+

European Journal of Mass Spectrometry ◽

10.1177/1469066718792902 ◽

2018 ◽

Vol 25 (1) ◽

pp. 97-111 ◽

Cited By ~ 5

Author(s):

Cameron J Owen ◽

Georgia C Boles ◽

Giel Berden ◽

Jos Oomens ◽

PB Armentrout

Keyword(s):

Amino Acid ◽

Gas Phase ◽

Single Point ◽

Basis Sets ◽

Side Chain ◽

Amine Group ◽

Linear Absorption ◽

Action Spectra ◽

Phase Structures ◽

Infrared Multiple Photon Dissociation

The gas-phase structures of zinc and cadmium complexes of lysine (Lys) are investigated via a combination of infrared multiple photon dissociation action spectroscopy and ab initio quantum chemical calculations. In order to unambiguously identify the experimentally observed species, [Zn(Lys−H)]+ and CdCl+(Lys), the action spectra were compared to linear absorption spectra calculated at the B3LYP level of theory, using 6-311+G(d,p) and def2-TVZP basis sets for the zinc and cadmium systems, respectively. Single point energies were also calculated at the B3LYP, B3P86, MP2, and B3LYP-GD3BJ (accounting for empirical dispersion) levels of theory using larger basis sets. Identification of the experimentally formed isomers is possible through good agreement between infrared multiple photon dissociation action spectra and the theoretically predicted spectra. The [Zn(Lys−H)]+ complex adopts a tridentate orientation involving the amino acid backbone amine and deprotonated carboxylic acid groups as well as the side-chain amine group, [Nα,CO−,Nɛ]. The CdCl+(Lys) complex similarly adopts a tridentate chelation involving the amino acid backbone amine and carbonyl groups, as well as the side-chain amine group, [Nα,CO,Nɛ]. In both cases, the identified complexes are the lowest energy gas-phase structures at all levels of theory.

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A long-term chemical and infrared spectroscopy study on a soil amended with municipal sewage sludge

Agronomie ◽

10.1051/agro:2001115 ◽

2001 ◽

Vol 21 (2) ◽

pp. 169-178 ◽

Cited By ~ 20

Author(s):

Giovanni Gigliotti ◽

Pier Lodovico Giusquiani ◽

Daniela Businelli

Keyword(s):

Infrared Spectroscopy ◽

Sewage Sludge ◽

Municipal Sewage ◽

Municipal Sewage Sludge ◽

Spectroscopy Study

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Polypeptides Folding: Rules for the Calculation of the Backbone Dihedral Angles φ starting from the Amino Acid Sequence

10.26434/chemrxiv.12000132 ◽

2020 ◽

Author(s):

Michele Larocca

Keyword(s):

Amino Acid ◽

Amino Acid Sequence ◽

Theoretical Approach ◽

Polypeptide Chain ◽

Hydrophobic Effect ◽

Side Chain ◽

Dihedral Angles ◽

Mechanical Forces ◽

Specific Chemical

<p>Protein folding is strictly related to the determination of the backbone dihedral angles and depends on the information contained in the amino acid sequence as well as on the hydrophobic effect. To date, the type of information embedded in the amino acid sequence has not yet been revealed. The present study deals with these problematics and aims to furnish a possible explanation of the information contained in the amino acid sequence, showing and reporting rules to calculate the backbone dihedral angles φ. The study is based on the development of mechanical forces once specific chemical interactions are established among the side chain of the residues in a polypeptide chain. It aims to furnish a theoretical approach to predict backbone dihedral angles which, in the future, may be applied to computational developments focused on the prediction of polypeptide structures.</p>

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Schistosomal Sulfotransferase Interaction with Oxamniquine Involves Hybrid Mechanism of Induced-fit and Conformational Selection

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190708103132 ◽

2020 ◽

Vol 16 (4) ◽

pp. 451-459 ◽

Cited By ~ 1

Author(s):

Fortunatus C. Ezebuo ◽

Ikemefuna C. Uzochukwu

Keyword(s):

Molecular Dynamics ◽

Amino Acid ◽

Binding Energy ◽

Binding Site ◽

Conformational Dynamics ◽

Side Chain ◽

Amino Acid Residues ◽

Conformational Selection ◽

Hybrid Mechanism ◽

Dynamics Simulations

Background: Sulfotransferase family comprises key enzymes involved in drug metabolism. Oxamniquine is a pro-drug converted into its active form by schistosomal sulfotransferase. The conformational dynamics of side-chain amino acid residues at the binding site of schistosomal sulfotransferase towards activation of oxamniquine has not received attention. Objective: The study investigated the conformational dynamics of binding site residues in free and oxamniquine bound schistosomal sulfotransferase systems and their contribution to the mechanism of oxamniquine activation by schistosomal sulfotransferase using molecular dynamics simulations and binding energy calculations. Methods: Schistosomal sulfotransferase was obtained from Protein Data Bank and both the free and oxamniquine bound forms were subjected to molecular dynamics simulations using GROMACS-4.5.5 after modeling it’s missing amino acid residues with SWISS-MODEL. Amino acid residues at its binding site for oxamniquine was determined and used for Principal Component Analysis and calculations of side-chain dihedrals. In addition, binding energy of the oxamniquine bound system was calculated using g_MMPBSA. Results: The results showed that binding site amino acid residues in free and oxamniquine bound sulfotransferase sampled different conformational space involving several rotameric states. Importantly, Phe45, Ile145 and Leu241 generated newly induced conformations, whereas Phe41 exhibited shift in equilibrium of its conformational distribution. In addition, the result showed binding energy of -130.091 ± 8.800 KJ/mol and Phe45 contributed -9.8576 KJ/mol. Conclusion: The results showed that schistosomal sulfotransferase binds oxamniquine by relying on hybrid mechanism of induced fit and conformational selection models. The findings offer new insight into sulfotransferase engineering and design of new drugs that target sulfotransferase.

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Synthesis and conformation of sequential basic polypeptides with branched and linear side chains

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19852925 ◽

1985 ◽

Vol 50 (12) ◽

pp. 2925-2936 ◽

Cited By ~ 2

Author(s):

Štěpánka Štokrová ◽

Jan Pospíšek ◽

Jaroslav Šponar ◽

Karel Bláha

Keyword(s):

Amino Acid ◽

Salt Concentration ◽

Salt Solution ◽

Theoretical Work ◽

Side Chain ◽

Amino Acid Residues ◽

Cd Spectra ◽

Low Salt ◽

Conformational Freedom ◽

Basic Polypeptides

Polypeptides (Lys-X-Ala)n and (Lys-X-Gly)n in which X represents residues of isoleucine and norleucine, respectively, and polypeptide (Tle-Lys-Ala)n, were synthesized via polymerization of 1-hydroxysuccinimidyl esters of the appropriate tripeptides to complete previously studied series. Circular dichroism (CD) spectra of the respective polymers were measured as a function of pH and salt concentration of the medium. The results were correlated with those obtained previously with the same series containing different amino acid residues at the X-position. The helix forming ability of the polypeptides (Lys-X-Ala)n with linear X side chain was found to be independent of the length. In the series (Lys-X-Gly)n the unordered conformation was the most probable one except (Lys-Ile-Gly)n. This polymer assumed the β conformation even in low salt solution at neutral pH. An agreement with some theoretical work concerned with the restriction of conformational freedom of amino acid residue branching at Cβ atom with our experimental results is evident.

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Comparison of the Potency of 8-L-Arginine, 8-D-Arginine and 8-D-Homoarginine Vasopressin Analogs with Substituted Phenylalanine in Position 2

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19941439 ◽

1994 ◽

Vol 59 (6) ◽

pp. 1439-1450 ◽

Cited By ~ 2

Author(s):

Miroslava Žertová ◽

Jiřina Slaninová ◽

Zdenko Procházka

Keyword(s):

Amino Acid ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Basic Amino Acid ◽

The Other ◽

Side Chain ◽

Inhibitory Potency ◽

Phase Synthesis ◽

Other Hand ◽

Order Of Magnitude

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.

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Analogues of the cholecystokinin octapeptide modified in the central part of the molecule

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19911963 ◽

1991 ◽

Vol 56 (9) ◽

pp. 1963-1970 ◽

Cited By ~ 3

Author(s):

Jan Hlaváček ◽

Václav Čeřovský ◽

Jana Pírková ◽

Pavel Majer ◽

Lenka Maletínská ◽

...

Keyword(s):

Amino Acid ◽

Biological Activities ◽

Point Of View ◽

Biologically Active ◽

Side Chain ◽

Amino Acid Residues ◽

Cholecystokinin Octapeptide ◽

Biological Tests ◽

Biological Potency ◽

Biologically Active Conformation

In a series of analogues of the cholecystokinin octapeptide (CCK-8) the amino acid residues were gradually modified by substituting Gly by Pro in position 4, Trp by His in position 5, Met by Cle in position 6, or the Gly residue was inserted between Tyr and Met in positions 2 and 3 of the peptide chain, and in the case of the cholecystokinin heptapeptide (CCK-7) the Met residues were substituted by Nle or Aib. These peptides were investigated from the point of view of their biological potency in the peripheral and central region. From the results of the biological tests it follows that the modifications carried out in these analogues and in their Nα-Boc derivatives mean a suppression of the investigated biological activities by 2-3 orders of magnitude (at a maximum dose of the tested substance of 2 . 10-2 mg per animal).This means that a disturbance of the assumed biologically active conformation of CCK-8, connected with a considerable decrease of the biological potency of the molecule, takes place not only after introduction of the side chain into its centre (substitution of Gly4), but also after the modification of the side chains of the amino acids or by extension of the backbone in further positions around this central amino acid.

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