The effect of replacing the ester bond with an amide bond and of overall stereochemistry on the activity of daptomycin

Moreira, Ryan; Barnawi, Ghufran; Beriashvili, David; Palmer, Michaël; Taylor, Scott D.

doi:10.1016/j.bmc.2018.12.004

Cited by 19 publications

(33 citation statements)

References 26 publications

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“…Although several resistant mutants were isolated, resistance development is still slower compared to drugs with single protein targets [163]. In contrast to well-characterized compounds like vancomycin, derivatives of daptomycin have not succeeded in making the transition into the clinic yet [12,[164][165][166][167]. This may at least partly be attributed to our limited understanding of its mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

“…Peptides carrying modifications at these positions exhibit up to five times higher minimal inhibitory concentrations (MICs) compared to unmodified daptomycin [11]. Another essential structural feature appears to be the ester bond between kynurenine and threonine [12]. Acidic residues are conserved in other calcium-dependent cyclic lipopeptides, for example friulimicin B and amphomycin A, emphasizing that complex formation with calcium and the resulting charge neutralization are essential features of this antibiotic class [13].…”

Section: Structure and Oligomerization Of Daptomycinmentioning

confidence: 99%

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More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

Gray

Wenzel

2020

Antibiotics

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Daptomycin is a cyclic lipopeptide antibiotic, which was discovered in 1987 and entered the market in 2003. To date, it serves as last resort antibiotic to treat complicated skin infections, bacteremia, and right-sided endocarditis caused by Gram-positive pathogens, most prominently methicillin-resistant Staphylococcus aureus. Daptomycin was the last representative of a novel antibiotic class that was introduced to the clinic. It is also one of the few membrane-active compounds that can be applied systemically. While membrane-active antibiotics have long been limited to topical applications and were generally excluded from systemic drug development, they promise slower resistance development than many classical drugs that target single proteins. The success of daptomycin together with the emergence of more and more multi-resistant superbugs attracted renewed interest in this compound class. Studying daptomycin as a pioneering systemic membrane-active compound might help to pave the way for future membrane-targeting antibiotics. However, more than 30 years after its discovery, the exact mechanism of action of daptomycin is still debated. In particular, there is a prominent discrepancy between in vivo and in vitro studies. In this review, we discuss the current knowledge on the mechanism of daptomycin against Gram-positive bacteria and try to offer explanations for these conflicting observations.

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Section: Discussionmentioning

confidence: 99%

Section: Structure and Oligomerization Of Daptomycinmentioning

confidence: 99%

More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

Gray

Wenzel

2020

Antibiotics

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“…The esterification coupling of activated C-terminal-N α -protected amino acid residue with HMBA was carried out using DIC/ HOBT as coupling agent. 4-dimethylaminopyridine (DMAP) was added to catalyze the formation of benzotriazole active ester in situ under microwave irradiation for 10 min at 75 o C [33].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Some Analogues of Polymyxin E1 Antibiotic Using Automated Solid Phase Peptide Synthesis Assisted With Microwave Irradiation

et al. 2019

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F IVE analogues of Polymyxin E1 antibiotic were synthesized via Fmoc-solid phase peptide synthesis (SPPS) strategy using Biotage® Initiator+Alstra™ microwave peptide synthesizer. The aim of this work is to study the importance of the cyclization conditions of the lactam ring on the purity and yield of the final compounds. For this purpose, replacing L-Thr10 with L-Asp allowed the application of different cyclization methodologies. In all analogues, the Dab5,8,9 residues were replaced with Arg, while the Dab4 residue involved in lactam cyclization was replaced with Lys. Modification of the linear tripeptide tail was applied to two of the analogues. The obtained compounds were characterized with different spectroscopic techniques and will be tested for their antimicrobial activity.

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“…The most popular route to protected AABA involves nucleophilic opening of a cyclic sulfamidate derived from threonine esters (96), as first reported by Chandrasekaran and co-workers. 85 Subsequent reports found that the reaction sequence tolerates Boc-, [85][86][87] Cbz-, 88 and benzyl-protected 87 -amines and methyl-, tBu-, and Bn-protected 89 carboxylic acids. The route is short, operationally simple, scalable, and the overall yields of products 97 are generally quite high.…”

Section: Review Synthesismentioning

confidence: 99%

“…Scheme 47 Albericio's synthesis of aza-kahalalide analogues using AABA as a synthon Taylor and co-workers used Fmoc-protected AABA to synthesize aza-analogues of daptomycin and A54145D to determine the impact of both the ester bond and the stereochemistry at the side chain of Thr on the antimicrobial activity. 86,171 For example, in their synthesis of daptomycin analogue 256 (Scheme 48), the AABA residue was incorporated into the linear peptide 254, which was then reduced to the corresponding peptide amine 255 using DTT/DIPEA/DMF. Trp was coupled on to the -amino group and the remaining amino acids (Glu and Ser) were appended…”

Section: Scheme 46 Synthesis Of Papuamide B Developed By Ma and Co-womentioning

confidence: 99%

Synthesis of Azido Acids and Their Application in the Preparation of Complex Peptides

Moreira¹,

Noden²,

Taylor³

2020

Synthesis

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Azido acids are important synthons for the synthesis of complex peptides. As a protecting group, the azide moiety is atom-efficient, easy to install and can be reduced in the presence of many other protecting groups, making it ideal for the synthesis of branched and/or cyclic peptides. α-Azido acids are less bulky than urethane-protected counterparts and react more effectively in coupling reactions of difficult-to-form peptide and ester bonds. Azido acids can also be used to form azoles on complex intermediates. This review covers the synthesis of azido acids and their application to the total synthesis of complex peptide natural products.1 Introduction2 Synthesis of α-Azido Acids2.1 From α-Amino Acids or Esters2.2 Via α-Substitution2.3 Via Electrophilic Azidation2.4 Via Condensation of N-2-Azidoacetyl-4-Phenylthiazolidin- 2-Thi one Enolates with Aldehydes and Acetals2.5 Synthesis of α,β-Unsaturated α-Azido Acids and Esters3 Synthesis of β-Azido Acids3.1 Preparation of Azidoalanine and 3-Azido-2-aminobutanoic Acids3.2 General Approaches to Preparing β-Azido Acids Other Than Azi doalanine and AABA4 Azido Acids in Total Synthesis4.1 α-Azido Acids4.2 β-Azido Acids and Azido Acids Containing an Azide on the Side Chain5 Conclusions

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The effect of replacing the ester bond with an amide bond and of overall stereochemistry on the activity of daptomycin

Cited by 19 publications

References 26 publications

More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

Synthesis of Some Analogues of Polymyxin E1 Antibiotic Using Automated Solid Phase Peptide Synthesis Assisted With Microwave Irradiation

Synthesis of Azido Acids and Their Application in the Preparation of Complex Peptides

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