Targeting Tumors Using Peptides

Abstract

To penetrate solid tumors, low molecular weight (Mw < 10 KDa) compounds have an edge over antibodies: their higher penetration because of their small size. Because of the dense stroma and high interstitial fluid pressure of solid tumors, the penetration of higher Mw compounds is unfavored and being small thus becomes an advantage. This review covers a wide range of peptidic ligands—linear, cyclic, macrocyclic and cyclotidic peptides—to target tumors: We describe the main tools to identify peptides experimentally, such as phage display, and the possible chemical modifications to enhance the properties of the identified peptides. We also review in silico identification of peptides and the most salient non-peptidic ligands in clinical stages. We later focus the attention on the current validated ligands available to target different tumor compartments: blood vessels, extracelullar matrix, and tumor associated macrophages. The clinical advances and failures of these ligands and their therapeutic conjugates will be discussed. We aim to present the reader with the state-of-the-art in targeting tumors, by using low Mw molecules, and the tools to identify new ligands.

Bifunctional Therapeutic Peptides for Targeting Malignant B Cells and Hepatocytes: Proof of Concept in Chronic Lymphocytic Leukemia

“…[16] Finally, in recent years, other TPP have been described and validated for precision tumor delivery. [9,17,18] Protein/proteins interactions (PPIs) are well recognized as promising therapeutic targets. [19] Given their physicochemical characteristics, interfering peptides (IPs) that modulate PPIs are better suited than small molecules to interfere with the large surface interactions in PPIs.…”

“…[ 16 ] Finally, in recent years, other TPP have been described and validated for precision tumor delivery. [ 9,17,18 ]…”

Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)

“…Cysteine is known to play a role in structural stability of cyclic peptides through the formation of disulfide bridge [28][29][30][31]. The original CX 7 C phage-displayed peptide library from which the CooP peptide was identified contained two cysteine residues which are important for the stabilization of the peptide structure [2,32]. A previous study showed that adding an extra cysteine residue to a cyclic nonapeptide, iRGD (CRGDK/RGPD/EC), improved the tumor penetrating function [33].…”

Metabolism of a Bioorthogonal PET Tracer Candidate [19F/18F]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

“… 9 SiFA chemistry is a radiofluorination strategy for fast and efficient radiolabeling of higher molecular weight constructs such as peptides, proteins, or nanoparticles that accumulate to tumors by enhanced permeability and retention (EPR) effect 10 , 11 or by targeted strategies. 12 − 14 Recently, a compound radiolabeled with SiFA chemistry, a somatostatin receptor-2 targeting peptide 18 F-SiFA lin -TATE, has entered clinical trials. 15 − 17 Main advantage of organophosphine fluoride acceptors or SiFA compounds lie in their tendency to undergo fast isotopic exchange (IE) of fluorine-19 to fluorine-18 ( 19 F/ 18 F), thus generating the 18 F-PET-radiotracer in minutes at ambient temperature.…”