New answers tagged optimization
Photoshops your best bet, although it doesn't like it if you use Save for Web on humongous images, you can just do a straight save if you want to keep your alpha channel. You don't say what the sprites are being used for but most game development API's support targeting one colour (say 255,255,0) as an alpha channel.
Adobe's Photoshop supports something like 300,000 pixel canvas's. It has a "Save for Web" feature that allows you to save a PNG24 file (which supports your alpha transparency). It too has all the functions you are looking for.
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