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

1985 ◽  
Vol 50 (12) ◽  
pp. 2925-2936 ◽  
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.

Conformation of branched polypeptides based on poly(L-lysine): Circular dichroism study

1980 ◽  
Vol 45 (3) ◽  
pp. 941-949 ◽  
Author(s):  
Hana Votavová ◽  
Ferenc Hudecz ◽  
Judit Kajtár ◽  
Mária Szekerke ◽  
Jaroslav Šponar ◽  
...  
Keyword(s):  
Circular Dichroism ◽  
Amino Acid ◽  
Main Chain ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Cd Spectra ◽  
Circular Dichroïsm

Circular dichroism (CD) spectra of branched (multichain) polypeptides based on poly(L-lysine) with DL-alanine and other amino-acid residues in the side chain have been measured under various conditions of pH. The spectra were interpreted using spectra of poly(L-lysine) as standard. No straightforward correlation between polypeptide CD spectra and their structure could be detected. The contribution of the side chain CD to that of the main chain is additive in some cases, but in other cases qualitatively different CD spectra arise. The reason for this CD behavior is discussed.

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

2020 ◽  
Vol 16 (4) ◽  
pp. 451-459 ◽  
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.

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

1991 ◽  
Vol 56 (9) ◽  
pp. 1963-1970 ◽  
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.

scholarly journals Effect of roasting temperature on lipid and protein oxidation and amino acid residue side chain modification of beef patties

RSC Advances ◽  
2021 ◽  
Vol 11 (35) ◽  
pp. 21629-21641
Author(s):  
Chao Xia ◽  
Pingping Wen ◽  
Yaming Yuan ◽  
Xiaofan Yu ◽  
Yijing Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Residue ◽  
Protein Oxidation ◽  
Relative Number ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Beef Patties ◽  
Lipid And Protein Oxidation ◽  
Roasting Temperature

The relative number of peptides modified by the amino acid residues of actin from raw beef patties and those cooked at different roasting temperatures.

scholarly journals Development of Antimicrobial Stapled Peptides Based on Magainin 2 Sequence

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 444
Author(s):  
Motoharu Hirano ◽  
Chihiro Saito ◽  
Hidetomo Yokoo ◽  
Chihiro Goto ◽  
Ryuji Kawano ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Amino Acid ◽  
Hemolytic Activity ◽  
Helical Structure ◽  
Antimicrobial Activities ◽  
Side Chain ◽  
Membrane Disruption ◽  
Amino Acid Residues ◽  
Electrophysiological Measurements ◽  
Cell Membrane Disruption

Magainin 2 (Mag2), which was isolated from the skin of the African clawed frog, is a representative antimicrobial peptide (AMP) that exerts antimicrobial activity via microbial membrane disruption. It has been reported that the helicity and amphipathicity of Mag2 play important roles in its antimicrobial activity. We investigated and recently reported that 17 amino acid residues of Mag2 are required for its antimicrobial activity, and accordingly developed antimicrobial foldamers containing α,α-disubstituted amino acid residues. In this study, we further designed and synthesized a set of Mag2 derivatives bearing the hydrocarbon stapling side chain for helix stabilization. The preferred secondary structures, antimicrobial activities, and cell-membrane disruption activities of the synthesized peptides were evaluated. Our analyses revealed that hydrocarbon stapling strongly stabilized the helical structure of the peptides and enhanced their antimicrobial activity. Moreover, peptide 2 stapling between the first and fifth position from the N-terminus showed higher antimicrobial activity than that of Mag2 against both gram-positive and gram-negative bacteria without exerting significant hemolytic activity. To investigate the modes of action of tested peptides 2 and 8 in antimicrobial and hemolytic activity, electrophysiological measurements were performed.

scholarly journals Glycine in Water Favors the Polyproline II State

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1121 ◽  
Author(s):  
Brian Andrews ◽  
Shuting Zhang ◽  
Reinhard Schweitzer-Stenner ◽  
Brigita Urbanc
Keyword(s):  
Amino Acid ◽  
Spectroscopic Data ◽  
Heavy Atom ◽  
Conformational Space ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Glycine Residue ◽  
Polyproline Ii ◽  
Conformational Preferences ◽  
Central Residue

Conformational preferences of amino acid residues in water are determined by the backbone and side-chain properties. Alanine is known for its high polyproline II (pPII) propensity. The question of relative contributions of the backbone and side chain to the conformational preferences of alanine and other amino acid residues in water is not fully resolved. Because glycine lacks a heavy-atom side chain, glycine-based peptides can be used to examine to which extent the backbone properties affect the conformational space. Here, we use published spectroscopic data for the central glycine residue of cationic triglycine in water to demonstrate that its conformational space is dominated by the pPII state. We assess three commonly used molecular dynamics (MD) force fields with respect to their ability to capture the conformational preferences of the central glycine residue in triglycine. We show that pPII is the mesostate that enables the functional backbone groups of the central residue to form the most hydrogen bonds with water. Our results indicate that the pPII propensity of the central glycine in GGG is comparable to that of alanine in GAG, implying that the water-backbone hydrogen bonding is responsible for the high pPII content of these residues.

scholarly journals Differentiating Amino Acid Residues and Side Chain Orientations in Peptides Using Scanning Tunneling Microscopy

2013 ◽  
Vol 135 (49) ◽  
pp. 18528-18535 ◽  
Author(s):  
Shelley A. Claridge ◽  
John C. Thomas ◽  
Miles A. Silverman ◽  
Jeffrey J. Schwartz ◽  
Yanlian Yang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Scanning Tunneling Microscopy ◽  
Side Chain ◽  
Scanning Tunneling ◽  
Amino Acid Residues ◽  
Tunneling Microscopy

scholarly journals Inhibition of human μ-calpain by conformationally constrained calpastatin peptides

2008 ◽  
Vol 389 (1) ◽  
pp. 83-90 ◽  
Author(s):  
José Pfizer ◽  
Irmgard Assfalg-Machleidt ◽  
Werner Machleidt ◽  
Norbert Schaschke
Keyword(s):  
Amino Acid ◽  
Sequence Alignment ◽  
Salt Bridge ◽  
Side Chain ◽  
Amino Acid Residues ◽  
High Potency ◽  
Conformationally Constrained ◽  
Linear Peptide ◽  
The Core ◽  
Oppositely Charged

Abstract The 27-mer peptide CP1B-[1–27] derived from exon 1B of calpastatin stands out among the known inhibitors for μ- and m-calpain due to its high potency and selectivity. By systematical truncation, a 20-mer peptide, CP1B-[4–23], was identified as the core sequence required to maintain the affinity/selectivity profile of CP1B-[1–27]. Starting with this peptide, the turn-like region Glu10(i)-Leu11(i+1)-Gly12(i+2)-Lys13(i+3) was investigated. Sequence alignment of subdomains 1B, 2B, 3B and 4B from different mammalians revealed that the amino acid residues in position i+1 and i+2 are almost invariably flanked by oppositely charged residues, pointing towards a turn-like conformation stabilized by salt bridge/H-bond interaction. Accordingly, using different combinations of acidic and basic residues in position i and i+3, a series of conformationally constrained variants of CP1B-[4–23] were synthesized by macrolactamization utilizing the side chain functionalities of these residues. With the combination of Glu(i)/Dab(i+3), the maximum of conformational rigidity without substantial loss in affinity/selectivity was reached. These results clearly demonstrate that the linear peptide chain corresponding to subdomain 1B reverses its direction in the region Glu10-Lys13 upon binding to μ-calpain, and thereby adopts a loop-like rather than a tight turn conformation at this site.

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