A comparative 1H-N.M.R. study of MurNAc-l-Ala-d-iGln (MDP) and its analogue murabutide: Evidence for a structure involving two successive β-turns in MDP
“…The other two structures are more extended and compute to higher (relative) energies of 10 and 15 kcal/mol, respectively, in the CVFF 6 force field. The second of the three candidates forms a γ-turn in the Ala residue which is not observed in solution, while the third has no intramolecular H-bonding and has the lowest values of V IV-I and V V-I (0.27 and 0.36 Å, respectively).…”
Section: Resultsmentioning
confidence: 97%
“…With these values three of the candidates were extracted and focused on as the most probable candidates, namely clusters no. 149, 340, and 825; they are outlined in Table including a comment describing intramolecular H-bonding (or its absence) in the structure which is given for comparison with the conformational analyses in solution. , The stereoviews of the structures are presented in Figure . 2 Stereoviews of the representatives of conformation cluster no.…”
Section: Resultsmentioning
confidence: 99%
“…For this paper the same procedure involving conformational search and clustering is employed for (i) muroctasin ( N 2-[( N -acetylmuramoyl)- l -alanyl- d -isoglutaminyl]- N 6 -stearoyl- l -lysine, IV , Figure ), a potent analogue with increased lipophilicity, (ii) murabutide , ( V , Figure ), an active analogue with esterified C-terminus, and (iii) the inactive rigidified analogue N -acetylmuramyl- l -alanyl-3-(carbomethoxymethyl)- d -proline methyl ester ( VI , Figure ) that has already been presented . In the case of IV the stearoyl aliphatic chain may influence the sampling of the conformational space in vacuo and is replaced by a methyl group.…”
The CCLUES method [Pristovšek et al.
J.
Chem. Inf.
Comput. Sci.
1995, 35, 633] is further refined; the
set
of 42 candidates for the bioactive conformation of the immunostimulator
muramyl dipeptide (MDP) obtained
in the first run from 1035 originally considered conformations is
reduced to the three most probable candidates.
The refinement is based on usage of additional information from an
inactive and two active analogues:
conformations of MDP that superpose well on at least one conformation
of the inactive analogue are excluded
from the set, while those that do not and additionally superpose well
on at least one conformation of the
active analogues become more probable candidates. The choice of a
final candidate for the bioactive
conformation is based on accessibilities of the chemical groups most
important for binding to the putative
receptor and values of energies calculated with explicit water
molecules; the energies of the candidate
conformations which differ up to 15 kcal/mol from the lowest-energy
conformation in vacuo are virtually
equalized by the effects of the aqueous medium.
“…The other two structures are more extended and compute to higher (relative) energies of 10 and 15 kcal/mol, respectively, in the CVFF 6 force field. The second of the three candidates forms a γ-turn in the Ala residue which is not observed in solution, while the third has no intramolecular H-bonding and has the lowest values of V IV-I and V V-I (0.27 and 0.36 Å, respectively).…”
Section: Resultsmentioning
confidence: 97%
“…With these values three of the candidates were extracted and focused on as the most probable candidates, namely clusters no. 149, 340, and 825; they are outlined in Table including a comment describing intramolecular H-bonding (or its absence) in the structure which is given for comparison with the conformational analyses in solution. , The stereoviews of the structures are presented in Figure . 2 Stereoviews of the representatives of conformation cluster no.…”
Section: Resultsmentioning
confidence: 99%
“…For this paper the same procedure involving conformational search and clustering is employed for (i) muroctasin ( N 2-[( N -acetylmuramoyl)- l -alanyl- d -isoglutaminyl]- N 6 -stearoyl- l -lysine, IV , Figure ), a potent analogue with increased lipophilicity, (ii) murabutide , ( V , Figure ), an active analogue with esterified C-terminus, and (iii) the inactive rigidified analogue N -acetylmuramyl- l -alanyl-3-(carbomethoxymethyl)- d -proline methyl ester ( VI , Figure ) that has already been presented . In the case of IV the stearoyl aliphatic chain may influence the sampling of the conformational space in vacuo and is replaced by a methyl group.…”
The CCLUES method [Pristovšek et al.
J.
Chem. Inf.
Comput. Sci.
1995, 35, 633] is further refined; the
set
of 42 candidates for the bioactive conformation of the immunostimulator
muramyl dipeptide (MDP) obtained
in the first run from 1035 originally considered conformations is
reduced to the three most probable candidates.
The refinement is based on usage of additional information from an
inactive and two active analogues:
conformations of MDP that superpose well on at least one conformation
of the inactive analogue are excluded
from the set, while those that do not and additionally superpose well
on at least one conformation of the
active analogues become more probable candidates. The choice of a
final candidate for the bioactive
conformation is based on accessibilities of the chemical groups most
important for binding to the putative
receptor and values of energies calculated with explicit water
molecules; the energies of the candidate
conformations which differ up to 15 kcal/mol from the lowest-energy
conformation in vacuo are virtually
equalized by the effects of the aqueous medium.
“…Earlier using 1 H-NMR and nuclear Overhauser effect spectroscopy, it was shown that MDP consists of two type II adjacent β-turns forming an S-shaped structure [43,44]. The first β-turn is formed by a C 10 hydrogen bonding between the Ala NH and the acetamido C = O of N -acetylmuramic acid.…”
Section: Resultsmentioning
confidence: 99%
“…The first β-turn is formed by a C 10 hydrogen bonding between the Ala NH and the acetamido C = O of N -acetylmuramic acid. The existence of the second β-turn is assumed by the presence of a free carboxamide group of isoglutamine [43,44]. Correlation between amide frequency and protein secondary structure found in the literature is listed in Table 2.…”
In this study, chemical transformations of benzyl ester of О-(phenyl-2-acetamido-2,3-dideoxy-1-thio-β-d-glucopyranoside-3-yl)-d-lactoyl-l-alanyl-d-isoglutamine (SPhMDPOBn) on the fumed silica surface were examined, and the surface complex structure was characterized by temperature-programmed desorption mass spectrometry (TPD-MS), infrared spectroscopy (FTIR) and electrospray ion trap mass spectrometry (ES IT MS). Stages of pyrolysis of SPhMDPOBn in pristine state and on the silica surface have been determined. Probably, hydrogen-bonded complex forms between silanol surface groups and the C = O group of the acetamide moiety NH-(CH3)-C = O…H-O-Si≡. The thermal transformations of such hydrogen-bonded complex result in pyrolysis of SPhMDPOBn immobilized on the silica surface under TPD-MS conditions. The shifts ∆ν of amide I band (measured from 1,626 to 1,639 cm−l for SPhMDPOBn in pristine state) of 33 and 35 cm−l which occurred when SPhMDPOBn was immobilized on the silica surface may be caused by a weakening of the intramolecular hydrogen bonding of the SPhMDPOBn because the interaction with the silica surface as hydrogen bond with silanol groups is weaker than that in associates.
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