Synthesis and Characterization of Cysteine-Based Dimer Peptides to Enhance Its Therapeutic Ability to Combat Alzheimer’s Disease
Primary Investigator (PI) Name
Mohammad Halim
Department
CSM – Chemistry and Biochemistry
Abstract
With a staggering six million Americans currently living with it and it being the seventh leading cause of death in the United States according to the CDC, Alzheimer’s disease (AD) is quite a scourge in modern therapeutic drug research. The biological basis for AD is quite profound, as sticky clumps of β-amyloid proteinb accumulate between neurons to form amyloid plaques, leading to widespread neuronal death and decreased cognitive function. The goal of this research is to design and develop dimer peptides using two peptides (NAPVSIPQ and IIGLMVGGVVIA) which showed to inhibit b protein aggregates. The interest of dimer peptides as the potential to be less susceptible to degradation by proteases when compared to their monomer counterparts. In addition, biological activity such as target affinity and potency can also increase because of dimerization. These peptides were synthesized using Liberty Blue peptide synthesizer using solid peptide synthesis protocol. High swelling ProTide resin with a loading value of 0.6 mmol/g was employed to support the growing peptide chain. To remove protecting groups, a cleavage cocktail containing 82.5% trifluoracetic acid was added to synthesized peptide, then placed in a hot water bath. After filtration of cleaved peptide, cold ether was added to allow peptide precipitation and lastly centrifugation. The precipitated peptide was dissolved with water and acetic acid and finally freeze dried. To confirm target peptide was successfully synthesized, prepared peptide sample solutions were analyzed by Liquid Chromatography-Mass Spectrometry. Successful synthesis of peptide analog with added cysteine residue (CNAP), was confirmed with intense peak at m/z at 927.48, corresponding to [M+H]1+. The linear peptide IIGLMVGGVVIA also synthesized and detected at m/z 571.35 and 1141.70, numbers that correlated to [M+2H]2+ and [M+H]+ charge states, respectively. These peptides will be further modified to develop dimer peptides and test their efficiency on fibral reduction and binding affinity.
Disciplines
Medicinal-Pharmaceutical Chemistry | Organic Chemistry
Synthesis and Characterization of Cysteine-Based Dimer Peptides to Enhance Its Therapeutic Ability to Combat Alzheimer’s Disease
With a staggering six million Americans currently living with it and it being the seventh leading cause of death in the United States according to the CDC, Alzheimer’s disease (AD) is quite a scourge in modern therapeutic drug research. The biological basis for AD is quite profound, as sticky clumps of β-amyloid proteinb accumulate between neurons to form amyloid plaques, leading to widespread neuronal death and decreased cognitive function. The goal of this research is to design and develop dimer peptides using two peptides (NAPVSIPQ and IIGLMVGGVVIA) which showed to inhibit b protein aggregates. The interest of dimer peptides as the potential to be less susceptible to degradation by proteases when compared to their monomer counterparts. In addition, biological activity such as target affinity and potency can also increase because of dimerization. These peptides were synthesized using Liberty Blue peptide synthesizer using solid peptide synthesis protocol. High swelling ProTide resin with a loading value of 0.6 mmol/g was employed to support the growing peptide chain. To remove protecting groups, a cleavage cocktail containing 82.5% trifluoracetic acid was added to synthesized peptide, then placed in a hot water bath. After filtration of cleaved peptide, cold ether was added to allow peptide precipitation and lastly centrifugation. The precipitated peptide was dissolved with water and acetic acid and finally freeze dried. To confirm target peptide was successfully synthesized, prepared peptide sample solutions were analyzed by Liquid Chromatography-Mass Spectrometry. Successful synthesis of peptide analog with added cysteine residue (CNAP), was confirmed with intense peak at m/z at 927.48, corresponding to [M+H]1+. The linear peptide IIGLMVGGVVIA also synthesized and detected at m/z 571.35 and 1141.70, numbers that correlated to [M+2H]2+ and [M+H]+ charge states, respectively. These peptides will be further modified to develop dimer peptides and test their efficiency on fibral reduction and binding affinity.