CruzFluor™ sm 6 (CFLsm6) family has the spectral properties similar to those of Cy5.5, IRDye 700 and Alexa Fluor® 680. Their fluorescence is pH-independent from pH 3 to 11. These characteristics make this new dye family more robust to pH-sensitive assays. In some cases CFLsm6-labeled peptides and nucleotides exhibit stronger fluorescence and higher photostability than the ones labeled with Cy5.5, IRDye 700 and Alexa Fluor® 680. In pairing with our CruzQuench™ 6 (CQ6), a variety of FRET peptides and nucleotides can be developed for detecting proteases and molecular beacons with enhanced sensitivity and stability.