Peptide name : D-melittin

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : D

Peptide length: 27

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : MTS assay

Assay time : 24-h

Activity : IC50 = 3.4 µM

Cell line : MDA-MB-435 DOX-R

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 2950.59 Dalton

Aliphatic index : 0

Instability index : 40.6519

Hydrophobicity (GRAVY) : 0.3556

Isoelectric point : 11.105

Charge (pH 7) : 4.7472

Aromaticity : 3.703

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : infinite

hydrophobic moment : 0

Missing amino acid : A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y

Most occurring amino acid : l

Most occurring amino acid frequency : 4

Least occurring amino acid : p

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (33., 18., 44.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)CN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C

1 : Lv S, et al. Development of D-melittin polymeric nanoparticles for anti-cancer treatment. Biomaterials. 2021; 277:121076. doi: 10.1016/j.biomaterials.2021.121076

Paper title : Development of D-melittin polymeric nanoparticles for anti-cancer treatment.

Doi : https://doi.org/10.1016/j.biomaterials.2021.121076

Abstract : Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens.