Conformational Restriction of Cyanine Fluorophores in Far-Red and Near-IR Range


Small molecule fluorescent probes are important tools in diagnostic medicine. Existing far-red and near-IR cyanine fluorophores (e.g. Cy5, Alexa 647, Cy7, ICG) are active in the far-red and near-range, but these agents suffer from modest quantum yields (brightness) which limit wide utility. It has been reported that the limited brightness of these fluorophores is due to an excited-state C-C rotation pathway.

The invention is directed to a new class of conformationally restricted cyanines that exhibit significantly improved quantum yield (3-4-fold increase in fluorescence quantum yield). These compounds are active in the long wavelength range (absorbance maxima = 661nm, emission maxima = 681nm). Additionally, these compounds are detectable at lower concentrations with concurrent improvements in signal to noise. While these compounds can be readily appended to antibodies and small-molecule based targeting motifs, these compounds are particularly useful for imaging procedures where photon count is limiting, e.g., FACS procedures, super resolution microscopy, and fluorescence guided surgery applications.

The invention is also directed to a generalized approach for synthesizing variants of the invention cyanine fluorophores prepared thus far.



Potential Commercial Applications: Competitive Advantages:
  • Fluorescence guided surgery 
  • Tumor visualization 
  • In vivo imaging
  • Fluorescent marker of the bile duct and ureter during abdominal surgery
  • Diagnostic medicine
  • Super resolution microscopy
  • FACS and other microscopy procedures where photon count is limiting
 
  • Improved quantum yield (3-4-fold increase in fluorescent emission over normal Cy5-type dyes (Absorbance maxima = 661 nm, Emission maxima= 681 nm, fluorescence quantum yield = 0.70)   
  • Excellent recovery from NaBH4 reduction 
  • Improved photon output in single molecule localization microscopy


Development Stage:
Pre-clinical (in vivo)

Related Invention(s):
E-271-2014
E-036-2018
E-139-2018


Inventors:

Martin Schnermann (NCI)  ➽ more inventions...

Megan Michie (NCI)  ➽ more inventions...


Intellectual Property:
Application No. 62/549,566

Publications:
Michie M, et al. Cyanine Conformational Restraint in the Far-Red Range.  PMID: 28862842

Collaboration Opportunity:

Licensing and research collaboration


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-143-2017
Updated: Jul 27, 2018