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Functionalisation of Dendrimers
Published in Neelesh Kumar Mehra, Keerti Jain, Dendrimers in Nanomedicine, 2021
Divya Bharti Rai, Deep Pooja, Hitesh Kulhari
Ongoing research in many fields is utilising proteins, peptides and even amino acids as a ligand for targeting a specific organ or tissue. Dendrimers have been conjugated with a wide range of amino acids, peptides and proteins. Therefore, dendrimer surfaces have been modified with these biomolecules for drug delivery purposes in cancer and human immunodeficiency virus (HIV) treatments. For example, Tuftsin, a tetrapeptide (Thr-Lys-Pro-Arg), increases natural killer activity of macrophages, monocytes and leukocytes by exhibiting specific binding to them. Tuftsin is an integral part of Fc portion of immunoglobulin IgG having dual advantages as a targeting ligand and phagocytosis inducer. Therefore, dendrimers with this peptide help in targeting and improving the therapeutic efficacy of the payload employed (Shukla et al. 2005).
Drug Targeting: General Aspects and Relevance to Nanotechnology
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Drug Delivery Approaches and Nanosystems, 2017
Preethi Naik, Megha Marwah, Meenakshi Venkataraman, Gopal Singh Rajawat, Mangal Nagarsenker
HIV infection is highly progressive and pestilent wherein the virus targets immune cells viz, CD4+ T cells, monocytes, macrophages, and dendritic cells. Explicitly targeting the unique markers on these cells is a propitious strategy for prophylactic or therapeutic effect. A number of approaches have emerged for confining drug molecules into HIV infected cells. Glycoporteins gp120, gp41 present on viral envelope are exposed on infected host cells which makes them an attractive target for cell specific delivery (Ramana et al., 2014). Immunoliposomes’ surface modified with ligand derived from Fab’ fragment of HIV-gp120-directed monoclonal antibody F105 reportedly facilitates specific uptake by nonphagocytic HIV infected cells (Clayton et al., 2009). Aptamers can also be used in lieu of antibodies to avoid loss in specificity owing to conformational changes involved in formulation steps of immunoliposomes. They are small molecules of oligonucleotides or peptides developed using SELEX (systematic evolution of ligands by exponential enrichment) and exhibit selectivity like antibodies with excellent structural stability (Brody and Gold, 2000). Chemokine receptor, CCR5 (co receptor for HIV) is expressed on T cells, macrophages, microglial cells, and dendritic cells (Lee et al., 1999). Natural ligand CCR5 (He et al., 1997), synthetic peptide (Agrawal et al., 2004), monoclonal antibodies (Trkola et al., 2001) are few molecules reported for targeting this receptor. Tuftsin, a tetrapeptide derived from IgG, targets its receptors in macrophages and dendritic cells, activating phagocytosis to attenuate HIV reservoirs in these cells (Jain et al., 2010; Tzehoval et al., 1978). Numerous glycan residues like mannose are exposed on the surface of HIV glycoprotein gp120 which makes carbohydrate binding agents congruent targeting ligands for these receptors (Ji et al., 2005; Pollicita et al., 2008; Ramana et al., 2014). Actinohivin found in Actinomycetes is one such agent reported (Hoorelbeke et al., 2010). Human leukocyte antigen receptor (HLA-DR) (Gray et al., 1999), C-type lectin DC-SIGN (DC specific ICAM-3-grabbing nonintegrin) (W. Jin et al., 2014) and LFA-1 (leukocyte function-associated antigen) (Hioe et al., 2011; Kim et al., 2010) are promising targets identified for HIV therapy.
Cloning, large-scale production and characterization of fusion protein (P-TUFT-ALT-2) of Brugian abundant larval transcript-2 with tuftsin in Pichia pastoris
Published in Preparative Biochemistry and Biotechnology, 2018
Rajkumar Paul, Selvarajan Karthik, Ponnusamy Vimalraj, Sankaranarayanan Meenakshisundaram, Perumal Kaliraj
Tuftsin is a naturally occurring nontoxic tetra-peptide immunopotentiator.[25] It increases the immunogenicity of an antigenic protein by directing it to phagocytic cells leading to a sturdier humoral and cellular immune response. Tuftsin has been used with various antigens such as malaria, leprosy, HIV, etc. in vaccine development.[26–28] Tuftsin along with DEC was found to suppress microfilarial stage of parasite till 90 days post treatment. Of great interest, DEC and tuftsin bearing liposomes were also observed as the most effective against adult parasites.[29] New batracylin conjugate with tuftsin derivative with branched side amino acid chain such as leucine or isoleucine exhibited 10-fold more cytotoxic effect on human tumor cell lines such as lung adenocarcinoma (A549) and myeloblastic leukemia (HL-60).[30]