|
1. |
Conformational characteristics of peptides and unanticipated results from crystal structure analyses |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 1-14
Isabella L. Karle,
Preview
|
PDF (709KB)
|
|
摘要:
AbstractPreferred conformation and types of molecular folding are some of the topics that can be addressed by structure analysis using x‐ray diffraction of single crystals. The conformations of small linear peptide molecules with 2–6 residues are affected by polarity of solvent, presence of water molecules, hydrogen bonding with neighboring molecules, and other packing forces. Larger peptides, both cyclic and linear, have manyintramolecularhydrogen bonds, the effect of which outweighs any intermolecular attractions. Numerous polymorphs of decapeptides grown from a variety of solvents, with different cocrystallized solvents, show a constant conformation for each peptide.Large conformational changes occur, however, upon complexation with metal ions. A new form of free valinomycin grown from DMSO exhibits near three‐fold symmetry with only three intramolecular hydrogen bonds. The peptide is in the form of a shallow bowl with a hydrophobic exterior. Near the bottom of the interior of the bowl are three carbonyl oxygens, spaced and directed so that they are in position to form three ligands to a K+, e.g., complexation can be completed by the three lobes containing the β‐bends closing over and encapsulating the K+ion. In another example, free antamanide and the biologically inactive perhydro analogue, in which four phenyl groups become cyclic hexyl groups, have essentially the same folding of backbone and side chains. The conformation changes drastically upon complexation with Li+or Na+. However, the metal ion complex of natural antamanide has a hydrophobic globlar form whereas the metal ion complex of the inactive perhydro analogue has a polar band around the middle. The structure results indicate that the antamanide molecule is in a complexed form during its biological activity.Single crystal x‐ray diffraction structure analyses have identified the manner in which water molecules are essential to creating minipolar areas on apolar helices. Completely apolar peptides, such as membrane‐active peptides, can acquire amphiphilic character byinsertion of a water moleculeinto the helical backbone of Boc‐Aib‐Ala‐Leu‐Aib‐Ala‐Leu‐Aib‐Ala‐Leu‐Aib‐OMe, for example. The C‐terminal half assumes an α‐helix conformation, whereas the N‐terminal half is distorted by an insertion of a water molecule W(1) between N(Ala5) and O(Ala2), forming and hydrogen bonds N(5)H ⃛ W(1) and W(1) ⃛ O(2). The distortion of the helix exposes CO (Aib1) and CO (Aib4) to the outside environment with the consequence of attracting additional water molecules. The leucyl side chains are on the other side of the molecule. Thus a helix with
ISSN:0006-3525
DOI:10.1002/bip.360280104
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
2. |
17O‐nmr studies of the conformational and dynamic properties of enkephalins in aqueous and organic solutions using selectively labeled analogues |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 15-26
Constantinos Sakarellos,
Ioannis P. Gerothanassis,
Nicolaos Birlirakis,
Theodoros Karayannis,
Maria Sakarellos‐Daitsiotis,
Michel Marraud,
Preview
|
PDF (695KB)
|
|
摘要:
AbstractThe synthesis of Leu‐enkephalin selectively17O‐enriched in Gly2and Gly3is reported. The17O‐nmr chemical shifts of [17O‐Gly2, Leu5]‐ and [17O‐Gly3, Leu5]‐enkephalins in H2O are almost identical and independent of the pH. Since hydrogen bonding is the dominant factor governing the chemical shifts of the peptide oxygen, it can be concluded that the hydration state of both oxygens is identical and independent of the pH. The17O chemical shifts of the [17O‐Leu5]‐enkephalin terminal carboxyl group at pH ∼ 1.9 and 5.6 are very different in H2O but very similar in CH3CN/DMSO (4:1) solution. This suggests that the protonation state of the carboxyl group at both pH values in CH3CN/DMSO solution is the same and consequently that Leu‐enkephalin exists in the neutral form at pH ∼ 5.6. In this organic mixed solvent system both Gly2and Gly3oxygen resonances exhibit a significant shift to high frequency by the same extent (Δδ ∼ 30 ppm). It is concluded that both peptide oxygens are not hydrogen bonded to an appreciable extent and that no specific 2 ← 5 hydrogen bonding exists to an appreciable extent. This conclusion is in agreement with the energy of activation for molecular rotation, as determined fromT1measurements, which was found to be almost identical for both [17O‐Gly2, Leu5]‐ and [17O‐Gly3, Leu5]‐enkephal
ISSN:0006-3525
DOI:10.1002/bip.360280105
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
3. |
A crystal molecular conformation of leucine‐enkephalin related to the morphine molecule |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 27-40
A. Aubry,
N. Birlirakis,
M. Sakarellos‐Daitsiotis,
C. Sakarellos,
M. Marraud,
Preview
|
PDF (867KB)
|
|
摘要:
AbstractLeucine‐enkephalin (Try1‐Gly2‐Gly3‐Phe4‐Leu5) has been crytallized as a trihydrate from water solution. X‐ray diffraction reveals a tightly folded molecular conformation with two fused βIII‐ (Gly2‐Gly3) and βI‐ (Gly3‐Phe4) turns. The Tyr1and Phe4aromatic rings have a close orthogonal arrangement analogous to the tyramine and cyclohexenyl rings in morphine. This suggests that the conformation found in the trihydrate crystal structure could be required for recognitio
ISSN:0006-3525
DOI:10.1002/bip.360280106
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
4. |
The renin–angiotensin system: An example of the study of linear peptides by x‐ray crystallography |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 41-49
Gilles Precigoux,
Mohamed Benkoulouche,
Serge Geoffre,
Preview
|
PDF (466KB)
|
|
摘要:
AbstractIn order to get information on the bioactive conformations of the endogenic renin substrate, a few peptide segments of angiotensinogen, along with a pepstatin analogue, were studied in the solid state by x‐ray crystallography. These results are compared with the conformations of acidic proteinase inhibitors observed at the level of the active site. Such a comparison allows us to point out some analogies and differences between the observed conformation for the peptide alone and the conformations on the active sites. The analysis of the results should be a good starting point for making hypotheses on the renin substrate bioactive conformation(s
ISSN:0006-3525
DOI:10.1002/bip.360280107
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
5. |
1H‐nmr studies of receptor‐selective substance P analogues reveal distinct predominant conformations in DMSO‐d6 |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 51-64
Dina Levian‐Teitelbaum,
Nancy Kolodny,
Michael Chorev,
Zvi Selinger,
Chaim Gilon,
Preview
|
PDF (812KB)
|
|
摘要:
AbstractProton nmr parameters are reported for DMSO‐d6solutions of two receptor‐selective substance P analogues: Ac[Arg6, Pro9]SP6‐11, which is selective for the NK‐1 (SP‐P) receptor and [pGlu6, N‐MePhe8]SP6‐11, which selectively activates the NK‐3 (SP‐N) receptor. Full peak assignments of both analogues were obtained by COSY experiments. The chemical shifts, coupling constants, and temperature coefficients of amide proton chemical shifts as well as NOESY effects and calculated side‐chain rotamer populations of Phe side chains are reported for both peptides. Analysis of coupling constants and temperature coefficients together with the nuclear Overhauser enhancement spectroscopy effects suggest that Ac[Arg6, Pro9]SP6‐11has atransconfiguration about the Phe8‐Pro9amide bond and the preferred conformation of this analogue has a type I β‐turn. The nmr data for [pGlu6, N‐MePhe8]SP6‐11suggest that this peptide exists as a mixture ofcis–transisomers in which thecisisomer can preferably adopt a type VI β‐turn conformation, and thetransisomer can adopt a γ‐turn conformation. There are indications that the two last turns are stabilized by a hydrogen bond between thesyncarboxa
ISSN:0006-3525
DOI:10.1002/bip.360280108
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
6. |
Conformationally constrained tachykinins: N‐methylated analogues of neurokinin A |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 65-67
P. Rovero,
V. Pestellini,
R. Patacchini,
P. Santicioli,
C. A. Maggi,
A. Meli,
Preview
|
PDF (192KB)
|
|
摘要:
AbstractLimited conformational constraints have been introduced in the sequence of the C‐terminal fragment of the peptide neurotransmitter neurokinin A by N‐methylation of individual peptide bonds, and the biological activities of the peptides thus obtained were evaluated in order to assess the effect of such conformational constraint on receptor selectivity. The analogue methylated in position 7 shows enhanced selectivity toward NK‐1 rec
ISSN:0006-3525
DOI:10.1002/bip.360280109
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
7. |
Conformational behavior of cyclic CCK‐related peptides determined by 400‐MHz1H‐nmr: Relationships with affinity and selectivity for brain receptors |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 69-79
P. Roy,
B. Charpentier,
C. Durieux,
A. Dor,
B. P. Roques,
Preview
|
PDF (579KB)
|
|
摘要:
AbstractThe conformational study of a homogenous series of cyclic analogues of CCK8, selective for central receptors, such as Boc‐X‐Tyr(SO3H)‐Nle‐D‐Lys‐Trp‐Nle‐Asp‐Phe‐NH2, where X =L‐Glu,D‐Glu, or γ‐D‐Glu, was performed by 400‐MHz1H‐nmr. The regular increase in affinity for central receptors when going from [L‐Glu] to [γ‐D‐Glu] is correlated to (a) an enhancement in internal flexibility of the cyclic moiety, (b) an external orientation of the tyrosine side chain, and (c) a restructuring of the C‐terminal part of the peptide. All these results could permit a modeling of biologically active conformation of CCK
ISSN:0006-3525
DOI:10.1002/bip.360280110
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
8. |
Selective agonists for receptors of substance P and related neurokinins |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 81-90
D. Regoli,
S. Dion,
N.‐E. Rhaleb,
N. Rouissi,
C. Tousignant,
D. Jukic,
P. D'Orleans‐Juste,
G. Drapeau,
Preview
|
PDF (584KB)
|
|
摘要:
AbstractNeurokinins and their receptors are a complex system consisting of at least three endogenous agents—substance P (SP), neurokinin A (NKA), and neurokinin B (NKB)—and their corresponding receptor types, respectively, NK‐1, NK‐2, and NK‐3. Investigations on receptors have been made using sensitive and fairly selective pharmacological preparations (the dog carotid artery for the NK‐1, the rabbit pulmonary artery devoid of endothelium for the NK‐2, and the rat portal vein for the NK‐3 receptor), and some natural peptides of mammalian and nonmammalian origin. Because of the nonselectivity of the natural peptides, analogues of the neurokinins have been found that act on one receptor only and show therefore high selectivity. The selective agonists [Sar9, Met(O2)11]SP, [Nle10]NKA (4–10), and [MePhe7]‐NKB have been used successfully for (a) characterizing the three neurokinin receptors, (b) identifying isolated organs whose responses to neurokinins depend on the activation of a single (monoreceptor systems) or of more than one (multireceptor systems) receptor, and (c) elucidating some of the physiological function of the three receptor types. It is suggested that NK‐1 mediate peripheral vasodilatation and exocrine secretions, NK‐2 stimulate bronchial muscles and facilitate the release of catecholamines, and NK‐3 promote the release of acetylcho
ISSN:0006-3525
DOI:10.1002/bip.360280111
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
9. |
Bioactive conformation of linear peptides in solution: An elusive goal? |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 91-107
Piero A. Temussi,
Delia Picone,
Maria A. Castiglione‐Morelli,
Andrea Motta,
Teodorico Tancredi,
Preview
|
PDF (1021KB)
|
|
摘要:
AbstractBioactive peptides of natural origin have, in general, short linear sequences, and are characterized by a large conformational flexibility. It is very difficult to study their conformation in solution since they exist, almost invariably, as a complex mixture of numerous conformers, most of which are extended. The so‐called bioactive conformation may be one of them, although the solvents used in solution studies often have properties drastically different from those of the biological system in which the peptide acts. There is, however, no simple way of identifying the bioactive conformation amid the many existing conformers.It is possible toapproacha solution to this problem using two distinct strategies: (a) Limiting the conformational freedom of the peptide, e.g., by increasing the viscosity of the solution and decreasing the temperature, in the assumption that the bioactive conformation is, even slightly, more stable than the others. (b) Trying to mimic in solution the physicochemical features of the more reliable receptor models.These two approaches will be illustrated with examples taken mainly from oploid peptide
ISSN:0006-3525
DOI:10.1002/bip.360280112
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
10. |
Pseudopeptides and β folding: X‐ray structures compared with structures in solution |
|
Biopolymers,
Volume 28,
Issue 1,
1989,
Page 109-122
André Aubry,
Michel Marraud,
Preview
|
PDF (773KB)
|
|
摘要:
AbstractIn order to restrain the flexibility of the peptide molecules and reduce their biodegradation, modifications of the main chain are now introduced in pseudopeptide analogues. Surprisingly, there is very little data on the conformational properties of these derivatives. We have examined pseudopeptide analogues of RCO‐X‐Y‐NHR′ model dipeptides in the depsi, N‐methylated, reduced, retro, α, β‐dehydro, β‐amino acid, and hydrazino series, in the solid state by x‐ray diffraction, and in solution by ir and1H‐nmr spectroscopy. This study provides us with accurate dimensions of the peptide surrogates, and gives some information on the conformational tendencies induced by these substitutions, with reference to those of the related
ISSN:0006-3525
DOI:10.1002/bip.360280113
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
|
|