Arginine-Rich Peptide Development for Stroke

The development of effective and safe neuroprotective drugs for the treatment of ischemic stroke remains an urgent unmet need. Cationic arginine-rich peptides (CARPs) are a novel class of neuroprotective agents that combine different properties that provide neuroprotective effects in the treatment of ischemic stroke. The guanidine group in arginine forms double-dentate hydrogen bonds with the negatively charged carboxyl, sulfate, and phosphate groups of proteins, mucopolysaccharides, and cell membrane phospholipids. They are highly anti-excitotoxic and anti-inflammatory neuroprotective effectiveness, interfere with calcium influx into the cell, stabilize mitochondria, inhibit protein hydrolytic enzymes, induce survival signaling, and reduce oxidative stress.

Fig. 1. Schematic representation of CARP neuroprotective mechanisms of action. (Meloni et al., 2020)

Our Arginine-Rich Peptide Development Services

Ace Therapeutics is a stroke-focused CRO with extensive expertise in the development of neuroprotective peptides. Our multidisciplinary team consists of leading medicinal chemists and pharmacologists with in-depth knowledge of peptide synthesis, structure-activity relationships, and drug development processes. We are your trusted partner in providing comprehensive services for the development of arginine-rich peptides for stroke.

Design and Synthesis of Arginine-Rich Peptides

We can perform high-throughput screening of peptide libraries containing more than thousands of different peptides. Our peptide synthesis laboratories are equipped with advanced instrumentation to synthesize CARPs with precision and efficiency. Since CARPs with different amino acid sequences or modifications will have different physicochemical and biological properties, we also provide customized new CARPs with more targeted molecular mechanisms of action to improve stroke outcomes.

• Polyarginine peptides, arginine-rich cationic cell-penetrating peptides (CCPPs) or protein-derived peptides
• Putative neuroprotective peptides fused to CCPPs
• Endogenous peptides

Our experts consider factors such as peptide length, charge, secondary structure, and arginine distribution to design protocols that optimize the ability of peptides to penetrate the blood-brain barrier and exert neuroprotective effects. We adhere to stringent quality control measures to ensure the purity, stability, and reproducibility of our synthetic peptides.

Evaluation of Arginine-Rich Peptides in Experimental Stroke Models

Our in vitro and in vivo evaluation platforms include advanced imaging systems, electrophysiological recording devices, and behavioral neuroscience equipment to provide a comprehensive evaluation of the efficacy and safety of arginine-rich peptides.

• Flow cytometry quantifies cellular uptake of arginine-rich peptides.
• Lactate dehydrogenase (LDH) release assays to measure membrane integrity and cell death.
• Effects of arginine-rich peptides on signaling pathways, gene expression, or other cellular processes are assessed by protein blotting, immunofluorescence, or qRT-PCR.
• Neurological deficit scores to assess the severity of neurological injury.
• Infarct volume measurement.
• Histological analysis of brain sections.
• Assessment of blood-brain barrier disruption.
• Various behavioral tests to assess the effect of arginine-rich peptides on functional recovery.
• Study of the absorption, distribution, metabolism, and excretion of arginine-rich peptides.

Ace Therapeutics collaborates with academic institutions and pharmaceutical companies to help them design, synthesize, optimize, and evaluate neuroprotective arginine-rich peptides. If you are interested in our services, please do not hesitate to contact us!

1. Meloni, B. P., et al. (2020). Cationic arginine-rich peptides (CARPs): a novel class of neuroprotective agents with a multimodal mechanism of action. Frontiers in neurology, 11, 108.