Polyamide based peptidodendrimer conjugates

[0010] One aspect of the present invention relates to a monofunctional peptidodendrimer conjugate comprising: a polyamide dendrimer conjugated with an HSV-1 envelope glycoprotein-derived peptide, wherein the peptide is a substituted or unsubstituted peptide selected from the group consisting of gB8, PgH, gC1, g1, and g2. [0011] A second aspect of the present invention relates to a pharmaceutical composition comprising, in a pharmaceutically acceptable vehicle, (i) a first monofunctional peptidodendrimer conjugate comprising: a polyamide dendrimer conjugated with a first HSV-1 envelope glycoprotein-derived peptide; and (ii) a second monofunctional peptidodendrimer conjugate comprising: a polyamide dendrimer conjugated with a second HSV-1 envelope glycoprotein-derived peptide, wherein the first and second HSV-1 envelope glycoprotein-derived peptides are different. [0012] A third aspect of the present invention relates to a bifunctional peptidodendrimer conjugate comprising: a polyamide dendrimer conjugated with two different HSV-1 envelope glycoprotein-derived peptides. [0013] The present invention is further directed to pharmaceutical formulations containing the monofunctional peptidodendrimer conjugate and/or the bifunctional peptidodendrimer conjugate. [0014] A fourth aspect of the present invention relates to a method of inhibiting entry of HSV-1 into a host cell. This method involves contacting the host cell, under conditions effective to inhibit entry of HSV-1 into the host cell, with: (i) a monofunctional peptidodendrimer conjugate as described herein; (ii) (a) a first monofunctional peptidodendrimer conjugate as described herein and (b) a second monofunctional peptidodendrimer conjugate as described herein, where the first and second monofunctional peptidodendrimer conjugates contain different HSV-1 glycoprotein-derived peptides; (iii) a bifunctional peptidodendrimer conjugate as described herein; or (iv) a combination thereof. [0015] A fifth aspect of the present invention relates to a method of treating or preventing HSV-1 infection in a subject. This method involves administering to the subject, under conditions effective to treat or prevent HSV-1 infection: (i) a monofunctional peptidodendrimer conjugate as described herein; (ii) (a) a first monofunctional peptidodendrimer conjugate as described herein and (b) a second monofunctional peptidodendrimer conjugate as described herein, where the first and second monofunctional peptidodendrimer conjugates contain different HSV-1 glycoprotein-derived peptides; (iii) a bifunctional peptidodendrimer conjugate as described herein; or (iv) a combination thereof. [0016] As demonstrated herein, peptidodendrimer conjugates containing monofunctional or bifunctional poly(amide)-based dendrimers functionalized with one or more peptides derived from HSV-1 envelope glycoproteins have the potential to inhibit HSV-1 infectivity.