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Optimized Microwave Assisted Synthesis of LL37, a Cathelicidin Human Antimicrobial Peptide

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Abstract

LL37, a human cathelecidin antimicrobial peptide comprising of 37 amino acids has emerged as one of the vital therapeutic peptides associated with a number of biological applications. In this context, we herein report a highly efficient and optimized methodology for the synthesis of LL37 through SPPS assisted by microwave power. Standard conditions employing uronium coupling reagents was unsatisfactory from the 20th amino acid residue onwards. A segmentation approach revealed that the amide bond formation between the Val and Ile was identified as the problematic coupling. It was found that DIC/OxymaPure in conjunction with THF as the solvent gave best results during manual coupling of 20th position Ile and required double coupling as revealed by HPLC and MALDI-TOF MS. In order to verify the synthesis, antibacterial testing was carried out and the results revealed comparable values with that of literature reported.

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Abbreviations

DCC:

N,N′-Dicyclohexylcarbodiimide

DIC:

N,N′-Diisopropylcarbodiimide

DIPEA:

N,N-Diisopropylethylamine

DMF:

N,N-Dimethylformamide

HATU:

1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxidhexafluorophosphate

HBTU:

N-[(1H-Benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate N-oxide

HOBt:

1-Hydroxybenzotriazole

PyBOP:

(Benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate

TFA:

Trifluoroacetic acid

THF:

Tetrahydrofuran

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Acknowledgments

The authors would like to thank the National Research Foundation, SA; Aspenpharmacare, SA; and the University of KwaZulu-Natal, Durban, SA for having funded this project. Authors declare no conflict of interest with the information contained in this work.

Conflict of interest

Authors declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Catalysis and Peptide Research Unit, Department of Pharmacy, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa

    Jyotibon Dutta, Suhas Ramesh, Siduduzo M. Radebe, Anou M. Somboro, Beatriz G. de la Torre, Hendrik G. Kruger, Fernando Albericio & Thavendran Govender

  2. Antimicrobial Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, 4001, South Africa

    Anou M. Somboro & Sabiha Y. Essack

  3. Institute for Research in Biomedicine and CIBER-BBN, 08028, Barcelona, Spain

    Fernando Albericio

  4. School of Chemistry, Yachay Tech, Yachay City of Knowledge, 100119, Urcuqui, Ecuador

    Beatriz G. de la Torre & Fernando Albericio

  5. School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4001, South Africa

    Fernando Albericio

  6. Department of Organic Chemistry, University of Barcelona, 08028, Barcelona, Spain

    Fernando Albericio

Authors
  1. Jyotibon Dutta
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  2. Suhas Ramesh
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  3. Siduduzo M. Radebe
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  4. Anou M. Somboro
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  5. Beatriz G. de la Torre
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  6. Hendrik G. Kruger
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  7. Sabiha Y. Essack
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  8. Fernando Albericio
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  9. Thavendran Govender
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Corresponding author

Correspondence to Thavendran Govender.

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Dutta, J., Ramesh, S., Radebe, S.M. et al. Optimized Microwave Assisted Synthesis of LL37, a Cathelicidin Human Antimicrobial Peptide. Int J Pept Res Ther 21, 13–20 (2015). https://doi.org/10.1007/s10989-014-9439-3

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