Complex formation with alkali and alkaline earth metal ions of cyclic octapeptides, cyclo(Phe‐Pro)4, cyclo(Leu‐Pro)4, and cyclo[Lys(Z)‐Pro]4

Kimura, Shunsaku; Imanishi, Yukio

doi:10.1002/bip.360221106

Cited by 15 publications

(9 citation statements)

References 9 publications

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“…Fig. 3 summarizes the effect of a subset of alkali metal salts examined, with attention to those reported to bind peptides and depsipeptides in solution (45)(46)(47)(48)(49)(50). Weakly coordinating counteranions were chosen for their respective alkali metal cation to promote solubility of the salt additive and interaction of the metal cation with the growing depsipeptide chain.…”

Section: Significancementioning

confidence: 99%

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Batiste

Johnston

2016

Proc. Natl. Acad. Sci. U.S.A.

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Macrocyclic small molecules are attractive tools in the development of sensors, new materials, and therapeutics. Within early-stage drug discovery, they are increasingly sought for their potential to interact with broad surfaces of peptidic receptors rather than within their narrow folds and pockets. Cyclization of linear small molecule precursors is a straightforward strategy to constrain conformationally mobile motifs, but forging a macrocycle bond typically becomes more difficult at larger ring sizes. We report the development of a general approach to discrete collections of oligomeric macrocyclic depsipeptides using an oligomerization/macrocyclization process governed by a series of Mitsunobu reactions of hydroxy acid monomers. Ring sizes of 18, 24, 30, and 36 are formed in a single reaction from a didepsipeptide, whereas sizes of 24, 36, and 60 result from a tetradepsipeptide. The ring-size selectivity inherent to the approach can be modulated by salt additives that enhance the formation of specific ring sizes. Use of chemical synthesis to prepare the monomers suggests broad access to functionally and stereochemically diverse collections of natural product-like oligodepsipeptide macrocycles. Two cyclodepsipeptide natural products were prepared along with numerous unnatural oligomeric congeners to provide rapid access to discrete collections of complex macrocyclic small molecules from medium (18) to large (60) ring sizes.Mitsunobu | total synthesis | collective | macrocycle | oligomerization I nterest in the preparation and use of small molecules exhibiting macrocyclic rings is growing at a tremendous pace, driving the development of new approaches, new chemical reactions, and the underlying chemistry and tools (catalysts) to support them. Historically, studies of macrocyclization reactions have been guided by natural products bearing unusually large carbocycles or mediumand large-ring lactones, amides, and ethers. Fragmentation reactions of polycyclic molecules have long played a role in access to medium-sized macrocycles, whereas macrocyclizations to lactones and amides are often accomplished from linear precursors at high dilution. Insofar as these efforts were typically driven by the goal to prepare a specific macrocycle, often in the form relevant to a natural product synthesis or an engineered constraint to a peptide, absent from the field is an approach that provides rapid access to collections (1) of natural product-like macrocycles, particularly from stereochemically complex, functionally rich, linear precursors (2-6).Pioneers in this area have recorded some success (Fig. 1). Esterification reactions of activated hydroxy acids have led predominantly to diolides, (7-10) and in a single case, oligolides (11). Amidation reactions of activated polypeptides were central to the preparations of macrocyclic peptides by Rothe and Kreiss (12,13) and Wipf and coworkers (14, 15), but they were low yielding and size nonselective. Burke and coworkers (16,17) have shown that the efficiency of an 18-membered oligol...

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Section: Significancementioning

confidence: 99%

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Batiste

Johnston

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The metal ion transport by cyclo(o-Leu-L-Pro) 4 (140 ,umol dm -3 ) through CH 2 Cl 2 or CHC1 3 membrane (20cm 3 ) was measured using U-shaped tube. 9 Metal chloride (10 mmol dm - 3 ) and picric acid (25 mmol dm - 3 ) were dissolved in aqueous phase I (15cm 3 , pH 7.2), and the ion transport was monitored by the absorption of picrate anion in aqueous phase II ( 15 cm 3 ). Calcium ion transport across the liposomal membrane by cyclo(o-Leu-L-Pro )4 (5-10 ,umol dm -3 ) was judged by fluorescence of chlorotetracyclin, which fluoresces upon coordination with a divalent metal cation.…”

Section: Methodsmentioning

confidence: 99%

“…It is contrasting that CD spectrum of cyclo(L-Leu-L-Pro) 4 in alcoholic solution ch11nged by the addition of K + . 3 The binding constant was calculated from the variation of the molar ellipticity of CD spectrum. Thus the binding constant of cyclo(o-Leu-L-Pro) 4 with Ba2+ was determined to be 400dm-3 mol-1 , which is nearly the same as 360 dm 3 mol-1 reported for cyclo(L-Leu-L-Pro) 4 /Ba 2 + complex.…”

Section: Conformational Properties Of and Metal Ionmentioning

confidence: 99%

“…Thus the binding constant of cyclo(o-Leu-L-Pro) 4 with Ba2+ was determined to be 400dm-3 mol-1 , which is nearly the same as 360 dm 3 mol-1 reported for cyclo(L-Leu-L-Pro) 4 /Ba 2 + complex. 3 The rate constant of complex formation of cyclo(o-Leu-L-Pro) 4 with Ba2+ in MeOH-H2 0 (95: 5, vjv) was determined from time-resolved ellipticity of CD spectrum to be larger than 2 x 10 3 dm 3 mol-1 min_,_ This is much larger than 0. 7 dm 3 mol-1 min -I reported for cyclo(L-Leu-L-Pro) 4 and Ba2+ .…”

Section: Conformational Properties Of and Metal Ionmentioning

confidence: 99%

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Polypeptides as Models for Membrane-Active Proteins

Imanishi

1985

Polym J

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A cyclic oligopeptide, linear sequential polypeptides, and glycopeptides were synthesized and their activities in lipid assemblies were investigated in relation to conformational properties. First, a cyclic octapeptide, cyclo(D-Leu-L-Pro)4 , transported efficiently Ba2+ across CHC1 3 membrane. It transported calcium picrate across a liposomal membrane, which was evidenced by the fluorescence of chlorotetracyclin dissolved in the interior of the liposome. Secondly, sequential peptides, Boc-(Leu-Leu-o-Phe-Pro).-OBzl (n=3 and 4), and a sequential polymer, poly(Leu-Lue-o-Phe-Pro) took 310 helix conformation in nonpolar organic solvent, and the polymer yielded an electric current under an electric field, when it was added to bilayer lipid membrane (BLM) composed of oxidized cholesterol. This result indicates the formation of pores on the BLM through which ions permeate. The pores were possibly formed by folding and intramolecular association of the sequential polymer with 310 helix conformation in BLM. Thirdly, a linear dipeptide Boc-Asp-e-Lys-OMe was prepared, in which the {)(-amino group of the Lys unit was protected with pyrene butyryl group as a fluorecent probe and the fl-carboxyl group of Asp unit was linked by an amide bond to 1-fl-amino-acetylglucosamine which interacts specifically with a lectin, wheat germ agglutinin (WGA). Liposomes containing the glycodipeptide were associated by the addition of WGA. The association did not occur by the addition of unspecific lectin, phytohemagglutinin. The fluidity of liposome decreased on adding the glycodipeptide, but was restored by the further addition of WGA. Similar phenomena were observed when Ca 2 + was added to liposomes containing a dipeptide without the sugar group.KEY WORDS cyclo(o-Leu-L-Pro)4 1 Ion Transport I Liposome I Poly(Leu-Leu-D-Phe-Pro) I 310 Helix I Ion Channel I Bilayer Lipid Membrane I Glycodipeptide I Wheat Germ Agglutinin I Patching I It has been widely recognized that cell is an epitome of life. Almost all life phenomena take place in cell membrane, and proteins or glycoproteins in cell membrane play an essential role in the life phenomena. Therefore, it may be helpful to use synthetic peptides as models for membrane-active proteins in understanding the mechanism of life phenomena.Muscle contraction, transmittance of neuro impulse, some of antibiotic actions, and generation of membrane potential take place as a result of ion permeation across cell membrane, which is mediated by ionophore. There are two types of ionophores, one of them being carrier ionophores and the other channel-forming ionophores. and ionic molecules across biomembrane. 1 In my laboratory, cyclo(L-Leu-L-Pro) 4 has been synthesized previously as a carrier ionophore model. 2 It bound alkali and alkaline-earth metal ions 3 and transported these ions efficiently across CHC1 3 membrane. 4 However, it did not transport metal ions across lipid membrane, which was ascribed to a slow complex formation with metal ions in the lipid membrane system. 4 Cyclo(o-Leu-L-Pro) 4 was expected to...

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“…Although a large number of proline containing cyclic peptides has been reported [14][15][16][17][18] to form complexes with metal ions, the de novo design of membrane ion-transporting macrocyclic peptides is still scarce. 19,20 In addition to proline, ion-transporting peptides harbor amino acids having lipophilic side chains.…”

mentioning

confidence: 99%

Design, synthesis, conformational and membrane ion transport studies of proline‐adamantane hybrid cyclic depsipeptides

et al. 2007

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The design, synthesis, conformational, crystallographic, and ion transport studies of 30‐membered, proline containing depsipeptides that incorporate the rigid low molecular weight lipophilic adamantane (Adm) building blocks are reported. The adamantyl groups provide the desired membrane permeability and conformational constraint for efficient transport in lipid membranes. The novel cyclic depsipeptides are: c[AdmC(O)Pro OCH2 CHRNHC(O)ProC(O) AdmC(O)ProC(O)NHCHRCH2 OProC(O)] where RH for A and RCONHAdm for B. Crystal structure analysis of A established that the two peptide segments are identical in formula and in conformation and that the peptides are bonded to the interleaving Adm at the 1 and 3 positions. However, the complete ring is highly asymmetric in shape since bonds for both Peptide‐Adm‐Peptide segments have the syn‐anti motif. Torsional angles for the connecting bonds to Adm are −162°, +71° and −169°, −48°. The irregular clamshell shape of the molecule has three internal CO moieties directed in a manner that could provide three Na+O ligands. While A exhibited negligible transport of Na+ ions across membranes, peptide B endowed with two additional adamantanes in the periphery did transport Na+ ions from outside to inside. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 471–478, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Complex formation with alkali and alkaline earth metal ions of cyclic octapeptides, cyclo(Phe‐Pro)₄, cyclo(Leu‐Pro)₄, and cyclo[Lys(Z)‐Pro]₄

Cited by 15 publications

References 9 publications

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Polypeptides as Models for Membrane-Active Proteins

Design, synthesis, conformational and membrane ion transport studies of proline‐adamantane hybrid cyclic depsipeptides

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