Construct including an anchor, an enzyme recognition site and an indicator region for detecting microbial infection in wounds
Inventors
GUSE, Jan Hinrich • Reisser, Martin • Pietrzik, Nikolas • Baeuerlein, Christiane • Eitel, Kornelia
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The disclosed technology relates to chemical entities for the detection of wounds, e.g., chronic wounds or infected wounds, including compositions, substrates, kits, dressing materials, and articles, and systems containing such compounds. The disclosed technology further relates to methods of using these compositions, kits and systems in diagnostic assays, and in the diagnosis and/or detection of chronic or infected wounds based on enzymatic action on specific moieties and/or reaction sites. The disclosed technology additionally relates to detection of pathogenic, e.g., bacterial and/or viral substances, such as enzymes and substrates, at the wound situs. Additional disclosure relates to methods of characterizing wounds based on expression of a plurality of markers and using such information to treat, manage, and follow-up patients suffering from chronic or infected wounds.
Core Innovation
The invention relates to chemical entities of Formula I comprising an anchor (A), an enzyme recognition site (R), and an indicator region (I). The anchor (A) comprises a fluorenylmethyloxycarbonyl group (Fmoc) linked to the N-terminus of the peptide, and the enzyme recognition site (R) comprises a peptide of from four to eight amino acids having an N-terminus and a carboxy terminus, with at least one enzyme-labile region.
The indicator region (I) comprises an alcohol-containing or amine-containing chromophore or chromophore precursor linked via an amide, ester, or carbonate bond to the carboxy terminus of the peptide. Further embodiments specify amino acid sequence patterns containing variable amino acids (X), variable repeat parameter y, and optional linking moiety (L) together with a label (Z) selected from indoxyl compounds, indole, naphthol, Fast Blue RR, and Remazol Brilliant Blue.
The document further describes multiplex chemical entities containing multiple enzyme recognition or reaction sites for simultaneous detection of multiple wound enzymes or markers, together with compositions, systems, kits, surfaces, and wound-dressing formats comprising Formula I compounds. It also describes support-material anchoring and immobilization concepts and solid supports for dye immobilization, including Sephabeads, Sephadex beads, epoxy-activated beads, silica gel, and Chemicell SiCore Amin beads.
Claims Coverage
Two independent claims define Formula I chemical entities built from an anchor (A), an enzyme recognition site (R), and an indicator region (I). Across the claims, the inventive features include an Fmoc-linked peptide anchor, an enzyme-labile peptide recognition site, and an indicator region chromophore or chromophore precursor linked to the peptide carboxy terminus, with further sequence and label constraints.
Formula I architecture with anchor, enzyme recognition site, and indicator region
A chemical entity comprising a compound of Formula I wherein A is an anchor, R is an enzyme recognition site, and I is an indicator region.
Fmoc-linked peptide anchor
The anchor (A) comprises a fluorenylmethyloxycarbonyl group (Fmoc) linked to the N-terminus of the peptide.
Enzyme-labile peptide recognition site
The enzyme recognition site (R) comprises a peptide of from four to eight amino acids having an N-terminus and a carboxy terminus, with at least one enzyme-labile region.
Indicator region chromophore linkage to the peptide carboxy terminus
The indicator region (I) comprises an alcohol-containing or amine-containing chromophore or chromophore precursor linked via an amide, ester, or carbonate bond to the carboxy terminus of the peptide.
Sequence-defined R-I label selection
R-I comprises sequence patterns XyAAPXy-Z, XyAAPXy-L-Z, XyAAP(V/F/A)Xy-Z, or XyAAP(V/F/A)Xy-L-Z, wherein each X is any amino acid, y is independently a number selected from 0 to 200, L is a linking moiety, and Z comprises an indoxyl compound, indole, naphthol, Fast Blue RR, or Remazol Brilliant Blue.
The claims center on Formula I compounds with an Fmoc anchor, an enzyme-labile peptide recognition site, and a chromophore-based indicator region linked through amide, ester, or carbonate bond chemistry, with further sequence parameters and selected indicator labels.
Stated Advantages
Enables early in-situ detection and monitoring of wound infection based on immune-derived enzyme markers prior to overt infection signs.
Improved diagnostic utility for multi-marker readouts based on multiplex detection of wound enzymes or markers.
Documented Applications
Diagnostic use in wound infection detection, including early in-situ detection and monitoring in chronic wounds.
Multiplex wound infection diagnosis for simultaneous detection of multiple wound enzymes or markers.
Integration into wound dressings.
Use in dipsticks.
Use in tube systems or tubing inserts.
Use in vacuum wound therapy.
Use on solid-phase printed supports and microarrays.
Diagnostic system use of Formula I compounds in compositions, systems, kits, surfaces, and wound-dressing formats.
Interested in licensing this patent?