Coding

Part:BBa_K4359004

Designed by: Ira Zibbu   Group: iGEM22_IISER_TVM   (2022-09-02)


Tumour homing peptide THP Pep-1 against SKBR3


Introduction

Tumor homing peptides (THPs) are oligopeptides, usually consisting of 30 or fewer amino acids that selectively bind to specific markers on tumour cells. They are discovered via phage display experiments from a pool of randomly generated peptides. THPs can be used to deliver cargo selectively to tumour cells, such as imaging agents or therapeutics. They can also be used to decorate drug carriers to target tumour cells. Their small size, low immunogenicity, high specificity and versatility makes them ideal for a variety of purposes.

Biology

THP Pep-1, CTGNQAAFC, is a THP against the HER2-positive breast cancer cell line SK-BR-3. THP Pep-1 was selected for binding to SK-BR-3, with MCF-10-2A as a control cell line for counter-selection. Cell binding studies further confirmed the specificity of THP Pep-1 for SK-BR-3 when compared to BT-474 cells and MCF-10-2A. The exact target(s) of THP Pep-1 are not precisely known. Docking studies performed in AutoDock Vina and GOLD suggested two potential targets- C5AR1 (Complement component 5a receptor 1) and CX3AR1 (Chemokine (C-X3-C motif) receptor 1). Both proteins are GPCRs that have been associated with metastasis and tumour progression in breast cancer. Further studies are required to confirm the target of the peptide. The THP Pep-1 sequence and its data is derived from reference [2].

THP Pep-1 has cysteine residues at the start and the end, which form a disulphide bond to produce a loop structure. Therefore this peptide requires disulphide bond-reducing machinery to achieve its correct confirmation.

Modelling

The structure of THP Pep-1 is not published anywhere. protein structure prediction was done using AlphaFold. The predicted structures are given below:

Predicted structures of THP

For an example of the usage of this part, see (BBa_K4359009)

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