Publication: Formation of curcumin-cell penetrating peptide conjugates and evaluation of their antimicrobial properties
Abstract
Geleneksel tıbba, özellikle bitki bazlı terapötiklere olan ilginin artması, doğal maddelere yönelik araştırmalara öncülük etmiştir. Bitki kökenli kurkumin molekülü, antioksidan, antimikrobiyal ve biyofilm inhibisyonu özelliklerine sahip zerdeçalda (Curcuma Longa L.) bulunan bir polifenol türevidir. Potansiyeline rağmen, düşük su çözünürlüğü, zayıf absorpsiyona yol açan zayıf biyoyararlanımı, nötr ve bazik pH'ta instabilite nedeniyle kullanımı genellikle sınırlıdır. Mevcut çalışma, kurkuminin bakır kullanarak hücre penetran peptide konjuge edilerek terapötik potansiyelini geliştirmeyi amaçlamaktadır. Bu amaçla, bakır asetat, pVEC ve pVEC2 peptitleri kullanılarak mononükleer kurkumin-bakır(II) kompleksi(1:1 mol) ve çeşitli kurkumin-bakır (II)-peptit(pVEC veya pVEC2) kompleksleri(1:1:1 mol) sentezlendi. Komplekslerin yapısal karakterizasyonu UV absorpsiyonu (432–456 nm aralığında maksimum absorpsiyon bandındaki değişim), FTIR spektroskopisi (ν(C=C) ve ν(C=O) gibi bantlardaki gerilme titreşimlerinin kayması) ve kütle spektrometre ile elde edildi. DLS ölçümleri (boyut ölçümü), kurkuminin nanopartiküller oluşturmak için peptitlerle kompleksleştiğini doğrulamıştır. Kurkuminin çözünürlüğü, pVEC ile kompleksleşme üzerine büyük ölçüde iyileşmiştir. Kinetik stabilite analizi, bakır asetat ve pVEC'nin birlikte kurkuminin stabilitesini arttırdığını gösterdi. Son olarak, sentezlenen komplekslerin biyolojik aktivitesi, Escherichia coli, Bacillus subtilis ve Staphylococcus aureus'da değerlendirildi. Sonuçlar, kurkumin peptitlerle kompleks oluşturduğunda kurkuminin minimum inhibitör konsantrasyonunun azaldığını göstermiştir. Tüm bu sonuçlarla, pVEC ile bir kompleks oluşumunun, kurkuminin özelliklerini terapötik uygulamalar için geliştireceğine inanıyoruz.
Growing public interest in traditional medicine, particularly plant-based therapeuticals, has led search towards natural substances. The plant-derived molecule curcumin is a polyphenol derivative found in turmeric (Curcuma Longa L.) with antioxidant, antimicrobial and biofilm inhibition properties. Despite its potential, its use is often restricted because of its poor water solubility and bioavailability which lead to poor absorption and instability in neutral and basic pH. The current work aims to improve the therapeutical potential of curcumin by conjugating it to a cell penetrating peptide using copper. To this end, copper acetate, pVEC and pVEC2 peptides were used to synthesize a mononuclear curcumin-copper(II) complex (1:1 mol) and various curcumin-copper(II)-peptide (pVEC or pVEC2) complexes (1:1:1 mol). The structural characterization of the complexes was achieved by UV absorption (shifting of absorption maximum band at 432–456 nm), FTIR spectroscopy (shifting of stretching vibrations of ν(C=C) and ν(C=O) etc.), and mass spectrometry. DLS measurements (size measurement) have confirmed the complexation of curcumin with peptides to form nanoparticles. Solubility of curcumin greatly improved upon complexation with pVEC. Analysis of kinetic stability showed that together copper acetate and pVEC enhanced the stability of curcumin. Finally, the biological activity of the synthesized peptide complexes was evaluated in Escherichia coli, Bacillus subtilis and Staphylococcus aureus. Results have indicated that minimum inhibitory concentration of curcumin decreased when curcumin was complexed with the peptides. With all these results, we believe that the formation of a complex with pVEC has improved its properties for therapeutic applications.
Growing public interest in traditional medicine, particularly plant-based therapeuticals, has led search towards natural substances. The plant-derived molecule curcumin is a polyphenol derivative found in turmeric (Curcuma Longa L.) with antioxidant, antimicrobial and biofilm inhibition properties. Despite its potential, its use is often restricted because of its poor water solubility and bioavailability which lead to poor absorption and instability in neutral and basic pH. The current work aims to improve the therapeutical potential of curcumin by conjugating it to a cell penetrating peptide using copper. To this end, copper acetate, pVEC and pVEC2 peptides were used to synthesize a mononuclear curcumin-copper(II) complex (1:1 mol) and various curcumin-copper(II)-peptide (pVEC or pVEC2) complexes (1:1:1 mol). The structural characterization of the complexes was achieved by UV absorption (shifting of absorption maximum band at 432–456 nm), FTIR spectroscopy (shifting of stretching vibrations of ν(C=C) and ν(C=O) etc.), and mass spectrometry. DLS measurements (size measurement) have confirmed the complexation of curcumin with peptides to form nanoparticles. Solubility of curcumin greatly improved upon complexation with pVEC. Analysis of kinetic stability showed that together copper acetate and pVEC enhanced the stability of curcumin. Finally, the biological activity of the synthesized peptide complexes was evaluated in Escherichia coli, Bacillus subtilis and Staphylococcus aureus. Results have indicated that minimum inhibitory concentration of curcumin decreased when curcumin was complexed with the peptides. With all these results, we believe that the formation of a complex with pVEC has improved its properties for therapeutic applications.