Peptide name : [D-Ala]- nocardiotide A

Source/Organism : Marine sponge

Linear/Cyclic : cyclic

Chirality : D

Peptide length: Not available

C-terminal modification: cyclic

N-terminal modification : D-alanin

Non-natural peptide information: None

Assay type : MTT assay

Assay time : 24h

Activity : IC50 : 52 μM

Cell line : HeLa

Cancer type : Not specified

Other activity : Not found

Amino Acid Composition Bar Chart : Not available

Molecular mass : Not available

Aliphatic index : Not available

Instability index : Not available

Hydrophobicity (GRAVY) : Not available

Isoelectric point : Not available

Charge (pH 7) : Not available

Aromaticity : Not available

Molar extinction coefficient (cysteine, cystine): Not available

Hydrophobic/hydrophilic ratio : Not available

hydrophobic moment : Not available

Missing amino acid : Not available

Most occurring amino acid : Not available

Most occurring amino acid frequency : Not available

Least occurring amino acid : Not available

Least occurring amino acid frequency : Not available

3D-structure: Not available

Secondary structure fraction (Helix, Turn, Sheet): Not available

SMILES Notation: Not available

Molecular descriptors: Not available

ADMET properties: Not available

1 : Maharani R, et al. Synthesis and anticancer evaluation of [d-Ala]-nocardiotide A. RSC Adv. 2024; 14:4097-4104. doi: 10.1039/d4ra00025k

Paper title : Synthesis and anticancer evaluation of [d-Ala]-nocardiotide A.

Doi : https://doi.org/10.1039/d4ra00025k

Abstract : Cancer is currently one of the biggest causes of death in the world. Like some microorganisms, cancer cells also develop resistance to various chemotherapy drugs and are termed multidrug resistant (MDR). In this regard, there is a need to develop new alternative anticancer agents. Anticancer peptides (ACPs) with high selectivity and high cell penetration ability are a promising candidate, as well as they are easy to modify. A cyclohexapeptide called nocardiotide A was isolated from the marine sponge Callyspongia sp., which is cytotoxic towards several cancer cells such as MM, 1S, HeLa, and CT26 cells. Previously, nocardiotide A was synthesized with a very low yield owing to its challenging cyclization process. In this study, we synthesized [d-Ala]-nocardiotide A as a derivative of nocardiotide A using a combination of solid phase peptide synthesis (SPPS) and liquid phase peptide synthesis (LPPS). The synthesis was carried out by selecting a d-alanine residue at the C-terminus to give a desired cyclic peptide product with a yield of 31% after purification. The purified [d-Ala]-nocardiotide A was characterized using HR-ToF MS and 1H and 13C-NMR spectroscopy to validate the desired product. The anticancer activity of the peptide was determined against HeLa cancer cell lines with an IC₅₀ value of 52 μM compared to the parent nocardiotide A with an IC₅₀ value of 59 μM. In the future, we aim to mutate various l-amino acids in nocardiotide A to d-amino acids to prepare nocardiotide A derivatives with a higher activity to kill cancer cells with higher membrane permeation. In addition, the mechanism of action of nocardiotide A and its derivatives will be evaluated.