Targeted delivery of antimicrobial agents
A cationic antimicrobial peptide (CAMP) conjugate is disclosed. The CAMP conjugate may be made by identifying a suitable carrier peptide; identifying a suitable antimicrobial agent; creating a conjugate by conjugating the peptide with the antimicrobial agent; and evaluating and refining the conjugate. The peptide may be short peptide based on the sequence of a CAMP, such as human β-defensin-3. The peptide can be directly connected to the antimicrobial agent or through a linker segment. The antimicrobial agent may be connected to the peptide or the linker segment through stable or cleavable bonding. The peptide may carry and facilitate the delivery of the conjugated antimicrobial agent to a microbe.
1. A method for delivering an antimicrobial agent to a microbe, comprising contacting the microbe with a cationic antimicrobial peptide (CAMP) conjugated to the antimicrobial agent, wherein the CAMP comprises the amino acid sequence RGRRSSRRKK (SEQ ID NO:3), and wherein the CAMP is connected to the antimicrobial agent directly or through a linker segment, the antimicrobial agent being connected to the CAMP or the linker segment through a stable or cleavable bond.
2. The method of claim 1 , wherein the CAMP comprises an amide group on the C-terminus.
3. The method of claim 1 , wherein the linker segment affixes the antimicrobial agent to the CAMP through acylation of the amino group of the N-terminus of the CAMP.
4. The method of claim 1 , wherein the antimicrobial agent is levofloxacin.
5. The method of claim 1 , wherein the antimicrobial agent is chloramphenicol.
6. The method of claim 1 , wherein the antimicrobial agent is a diazeniumdiolate.
7. The method of claim 1 , wherein the linker connects the antimicrobial agent to the CAMP via an amide bond between a carboxyl group of the linker and a side chain of a lysine residue of the CAMP.
8. The method of claim 1 , wherein the antimicrobial agent or the linker is attached to the CAMP via an amide bond formed with a primary amino group of at least one of the N-terminus of the CAMP and a lysine side chain of the CAMP.
9. The method of claim 1 , wherein the microbe is a bacteria.
10. The method of claim 1 , wherein the microbe is a fungus.
11. The method of claim 1 , wherein the microbe is a virus.